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FRAUNHOFER INSTITUTE FOR CELL THERAPY AND IMMUNOLOGY
FRAUNHOFER IZI
SERVICE CATALOG
Fraunhofer IZI Service Catalog | 1
TABLE OF CONTENTS
Preface ........................................................................... 4
Annex (separate)
Navigation Introduction .................................................. 5
Table of Contents in Four
Categories:
Complex Product List
– indications
– competencies
Monoclonal Antibodies ................................................... 6
– technologies
Human-transgene Disease Models ................................ 10
– working groups
GxP-Services ................................................................. 13
Biobanken .................................................................... 16
Single Products
Biomarker and Test Development .................................. 18
Glossary
General Information
Fraunhofer Gesellschaft ................................................ 22
Prole of the Fraunhofer IZI........................................... 24
Research Environment Leizig ......................................... 28
Research Contracts ....................................................... 31
Contact ........................................................................ 32
How to Reach Us .......................................................... 34
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PREFACE
NAVIGATION
INTRODUCTION
Dear Reader,
How Can I Use the Fraunhofer IZI Service Catalog?
With this catalog, the Institute for Cell Therapy and Immunology in Leipzig would like
What Will I Find in the Product Description?
Browse and Peruse
The Product
Gain a general overview of the services and
You will nd unique features, the method and
products on offer at Fraunhofer IZI.
potential applications of each product or service.
the youngest branch of the Fraunhofer-Gesellschaft. The apparent dynamic growth of
To ease your way, the entries are in alphabetical
A reference project is also included for illustra-
the life science branch conrms the need for support of this branch by the Gesellschaft.
order.
tion.
Sciences Alliance.
Targeted Search
Useful Information
We are also pleased to draw your attention to the special events which we at Fraunhofer
You can search for a specic product of service
– list of additional products and services for
IZI regularly support. These are the World Conferences for Regenerative Medicine and
according to your individual needs.
to present to you its technological potential as well as the spectrum of cooperation
possibilities.
As a member of the Life-Science-Alliance of the Fraunhofer-Gesellschaft, we belong to
Modern biotechnology and the health care industry as well as active agent development,
food technology and regenerative medicine are main points in the Fraunhofer Life
– associated products at Fraunhofer IZI
the annual Life-Science-Symposia Leipzig, which take place at the Fraunhofer IZI. You
can nd more detailed information about both events on the Fraunhofer IZI homepage.
each working group
To help you nd your solution more quickly, the
– information about each working group
Fraunhofer IZI Service Catalog is divided into
– information about Fraunhofer IZI
For additional information about our working groups, reference projects and the devel-
four categories:
– contact names and information
opment of the institute, we would be pleased to send you a copy of our current annual
– indications
report, on request. The annual report is also available on our homepage, if you prefer.
– competencies
– technologies
We would be pleased to hear your impressions of this service catalog: tell us how we
– working groups
can improve it or make it more useful for you. The special product descriptions of the
working groups will also be continually updated in the Internet on the Fraunhofer IZI
Each category has its own index.
homepage.
Find the right product in the index list and turn
It would be our pleasure to visit you, to present selected approaches and product and
to the description in the alphabetically sorted
process developments, in person.
product section.
Leipzig, April 2009
We always strive to update and expand our range of products and services for you. The latest
version you can always nd on www.izi.fraunhofer.de/izi_leistungsangebot.html or respectively on
www.izi.fraunhofer.de/izi_downloads.html
Prof. Frank Emmrich
Head of Institute
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COMPLEX PRODUCT LIST:
MONOCLONAL ANTIBODIES
Antibodies
The high specicity with which antibodies recognize antigens makes them especially
interesting instruments in biology as well as in medical research and application.
The Fraunhofer IZI develops and produces antibodies for therapeutic and diagnostic
applications.
So far, therapeutic antibodies have been used primarily in various tumor types and
lymphomas, to treat rheumatoid arthritis, Morbus Chrohn, asthma and for prophylactic
treatment against rejection reactions after organ transplantation.
Applications (Selected)
Besides the diagnostic and therapeutic applications, antibodies can be used in diverse
ways in modern research, for example:
– immunohistochemistry: detection of target molecules in tissue samples
– ELISA: quantication of antigens and antibodies in liquid samples
– ELISPOT: detection of antigen or antibody secreting cells
– FACS: quantication of cells
– phagen display
– pregnancy tests
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Research
Production
Development
The value chain begins with a qualied investigation and
The institute offers various possibilities for producing
If positively evaluated, the target molecule, according to
market analysis of the customer’s eld of application. This
larger quantities of custom antibodies. Fraunhofer IZI
the customer’s wishes, will be identied and appropriate
entails the identication of competing products and an
has established production programs for recombinant,
epitopes will be developed and tested. The examination
estimate of the potential market share of the customer’s
polyclonal and monoclonal antibodies. Furthermore, the
includes cell function tests as well as in vivo testing.
product. Gaps in the market will be ascertained and
antibodies can be optimized and / or labeled through
Appropriate model-test systems are available in-house at
approaches will be prepared for the customer.
molecular biological processes.
Fraunhofer IZI. Following this step, a feasibility study will
determine the efcacy of the developed antibody on a
small-scale.
Documentation
Production Process
If the feasibility study shows that the developed antibody
Following the development of the GMP-conform process,
meets the customer’s needs, the process will be revised to
the production follows under GMP conditions. A special
meet GMP requirements and documented. Appropriate
strength at Fraunhofer IZI is producing clinical investiga-
The institute supports the design and performance of
protocols and SOPs will be produced.
tional new products according to §13 Arzneimittelgesetz
Phase II and III clinical studies.
Clinical Studies
(German Drug Law) fully GMP-conform. Furthermore,
master and working cell banks have been GMP-conform
established and stored, in order to later supply customers
with series production.
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COMPLEX PRODUCT LIST:
HUMAN-TRANSGENE DISEASE MODELS
Animal models have been integral in discovering the
HuI-Mouse
mechanisms of pathogenesis in human diseases, however
increasingly animal models have been critical in the
The human-immune (HuI) mouse possesses a complete
preclinical testing of new or improved active agents or
human immune system that has developed in an immune-
agent combinations.
defective mouse. The mouse regains its ability to react
immunologically. The antibody production as well as the
Provided very specic agents are developed, the target
cellular immune reactions are effected by a cooperative
molecules differ so signicantly in humans and test animal
effort of human immune cells. This has provided the
that no binding or comparable inuence can be detected.
opportunity to test diverse ligands that inuence human
This is often the case, for example, for monoclonal
immune cells – either stimulating or suppressing.
antibodies, soluble receptor molecules or more complex
Furthermore, on the basis of this model, different disease
peptide agents. In these instances, the alternatives are
correlates can be developed. This system is in continual
either to forego animal experiments or to examine
development with the University of Leipzig and as a
structurally similar binding partners. As experience has
technology platform is a unique feature.
shown that structurally similar molecules from different
species are not always functionally similar, false conclu-
The HuI system is also of particular interest for oncology,
sions are likely to result from such examinations.
because the interaction between human immune cells
and autologous tumor cells can take place in the test
Therefore, it has become a goal to test human molecules
mouse. Thereby it becomes possible to test the inuence
or cell aggregates in the system biological context. With
of new cytostatics and other anti-tumor agents not only
its cooperation partners, notably the University of Leipzig,
on tumor cells, but also on human immune cells in the
the Fraunhofer IZI offers innovative animal model systems
same system. Thus, one can examine if and how the
to meet this goal. It is also of interest to the institute to
immune system is affected. Furthermore, modulators and
develop further models according to customer needs.
stimulators for the human immune system can be tested
where a positive inuence on the immune answer against
tumor cells is assumed.
CD4- / DR-Mouse
The T-cell receptor complex with its associated accessory
molecules is one of the most complicated recognition and
signal transduction mechanisms in mammalian biology.
Human CD4 and MHC2 transgene mice make it possible
to examine MHC2 restricted peptides as well as ligands
for human CD4 in the mouse. The human molecules are
used similarly with respect to their distribution and accessibility, but also in view of their signaling characteristics.
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COMPLEX PRODUCT LIST:
GXP SERVICES
GLP Services
Services
“Good Laboratory Practice (GLP) is a quality system con-
– contract based research from concept to
cerned with the organisational process and the conditions
proof-of-principle
under which non-clinical health and environmental safety
– development of therapeutic agents
studies are planned, performed, monitored, recorded,
– new diagnostic systems and technologies for the
archived and reported.“
application of medicaments
– biosensor and biochip technologies
This is the denition of “Good Laboratory Practice“ in
the “OECD Principles of Good Laboratory Practice“ which
were then transposed into EC Directives and, after that,
into German law as Annex 1 of the German Chemicals
Act. The entire sixth section of the Chemicals Act is
devoted to Good Laboratory Practice. In paragraphs 19a
– preclinical evaluation of therapeutics for humans and
animals
– adherence to national, EU and FDA directives and
guidelines
– all development and evaluation processes under GLP
conditions
to 19d the scope and type of monitoring of GLP are laid
down by law.
As a consequence of its global implementation and largely
mutual recognition of test data, GLP has contributed more
than any other quality system to health, environmental
and animal protection. (Source: Federal Institute for Risk
Assessment)
Fraunhofer IZI possesses a separate GLP laboratory and
trained expert personnel. Our established technical
and human resources can completely cover integrated
research and development solutions.
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GMP Services
Services
GCP Services
Since Summer 2006, Fraunhofer IZI maintains its own
– process and protocol development for GMP conform
GCP comprises an internationally valid guideline for con-
development must be carried out in accordance with
ducting clinical studies. These guidelines include ethical
GCP guidelines. Foremost in the guidelines is always
and scientic aspects.
the protection of the patients or test persons. Important
New substances can only be submitted for approval
after a successful Phase III study. All phases of clinical
GMP conform clean room facility.
processes
– GMP production of diverse cell therapeutic products
The exible design of the production site makes the
(autologous and allogenic cell therapeutics, e.g. tissue
facility attractive for biotechnology companies that are
replacement / tissue engineering products, adult stem
Clinical studies are divided into three phases.
patient insurance and the exact documentation of the trial
cells, tumor vaccines, gene therapeutics)
– Phase I: Safety testing of new medicaments/therapies
results. Beyond these elements, GCP regulates the division
– Phase II: Testing the efcacy of new medicaments /
of responsibilities (Sponsor, Monitor, Principal Investigator,
bringing newly developed agents and therapeutics into
the clinical setting via clinical trials. The facility is divided
– GMP production of biologicals via mammalian cells on
into different suites. Each suite has its own class C clean
the scale of a phase I-early phase II clinical study or
room (preparation), own air locks from class C to class
preclinical testing (e.g. therapeutic recombinant
B (personnel, material transport) and two class B clean
rooms each (aseptic production). Class A is provided by
the safety benches in the B-rooms. The majority of the
available clean room suites are specialized for processes
related to the production of human autologous or allogenic cell therapeutics (e.g. tissue engineering products,
stem cell preparations, tumor vaccines). One suite is
designed for the production of therapeutic recombinant
proteins and antibodies in small quantities (preclinic,
phase I to early phase II). Besides the clean rooms and
the technical and regulatory infrastructure, Fraunhofer IZI
glycoproteins and monoclonal antibodies)
elements are the patient consent forms / declarations,
therapies (Phase IIa) and dose determination (Phase IIb)
– Phase III: To generate a signicant demonstration of
efcacy (also called Pivotal-Study)
Contract Research Organization, Ethics Commission) as
well as the quality management and required notication
of adverse events.
– advising for the establishment and validation of GMP
conform production processes
– support for the acquisition of a manufacturing
authorization according to §13 of the AMG
– provision of separate clean room suites for autonomous production of pharmaceutical products
– project transfer from research and development to
GMP conform production processes
– production, cryoconservation and storage of
pharmaceutical master and working cell banks
Fraunhofer IZI carries out studies in cooperation with
doctors and SMOs (Site Management Organizations) on
behalf of sponsors. The institute focuses on studies mainly
in ambulant care. Fraunhofer IZI is a dependable partner
in study planning, generating study protocols and all
relevant documentation for the submission to regulatory
authorities and ethics commissions. Examinations are
conducted on-site in cooperation with private doctors and
SMOs.
offers assistance in the building up and validation of GMP
conform production processes as well as obtaining an
ofcial manufacturing authorization according to §13 of
the AMG.
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COMPLEX PRODUCT LIST:
BIOBANKS
Biobanks are ordered collections of biological samples i.e.
Biobanks have the following aims:
micro organism, animals and plants. This includes complex
– development of new and optimization of existing
molecules as well as cells, tissue or organs which are con-
diagnostic tools
served or cryopreserved according to a specic protocol
– improve the clinical monitoring of chronic diseases
for long term storage. Biobanks that store human cells
– provision of cell systems for the optimization of
and tissue for medical purposes are of particular interest.
therapeutic approaches (e.g. for oncology)
– development and validation of disease preventing
With specialized technical equipment as well as unique
methods
biological-medical expertise, the Fraunhofer IZI is
able implement customized concepts for biobanking.
Biobanks are especially useful tools for new hybrid
The institute is actively researching in exploring new
disciplines which are in development. This includes
cryopreserving agents and techniques for cells and tissue
prevention research as well as regenerative medicine
preservation. We are able to isolate specialized cells of
and personalized medicine. The latter will allow custom-
normal and pathologically altered tissue through a wide
made treatments for patients. This includes analysis of
variety of isolation methods such as owcytomic cell
responsiveness to certain medications as well as risk
sorting. We have developed technology platforms to
analyses e.g. tendencies of patients to exhibit specic
isolate special types of stem cells from their surrounding
side effects.
tissue e.g. tumor stem cells.
With its interlocking competencies and research connecTo build and maintain a biobank special expertise is
tions to other Fraunhofer facilities who offer an array of
needed. The Fraunhofer IZI has professional expertise
technologies that complement ours Fraunhofer IZI offers:
in the isolation, characterization and preservation of
– design and assembly of custom made biobanks
biological samples as well as in the thawing and utilization
– storage of reference sample collections
process required for later use. We are also adept in the
– utilisation and access to Fraunhofer IZI biobanks for
documentation and electronic data management process
inammatory cells and tumor stem cells
and we provide consent forms for volunteers and patients
as well as consulting regarding bioethical and data safety
issues.
Fraunhofer IZI provides
– consulting in the construction of biobanks
– technical support in building and maintaining biobanks
– assembling handling services of customer biobanks
located at the Fraunhofer IZI
– utilisation of IZI biobanks
– storing reference samples for a customer
Biobanks are becoming an increasingly important research
tool through advances in modern analysis methods.
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COMPLEX PRODUCT LIST:
BIOMARKER AND TEST DEVELOPMENT
Biotechnological and biomedical research as well as
Equipment
preclinical and clinical studies require dependable high
throughput analyses to detect biomarkers, active agents
– custom microarray platforms
and genes.
– high throughput RT PCR
– Affymetrix
Thereby it is becoming increasingly crucial to analyze
– Combimatrix
samples of the most different origins quickly, precisely
– Agilent Bioanalyzer System
and, where possible, extensively. As variations in customer
– Caliper / Xenogen Imaging System
demand are so signicant, the development of a universal
– bioreactor
test recedes further and further. Fraunhofer IZI packages
– MoFlo II high speed cell sorter
competencies into one entity, in order to present partners
with comprehensive analytical possibilities. Through the
institute’s cooperation with partners, existing technology
platforms can be adapted to the individual needs of
customers or fully novel test methods can be developed.
Whether used for agent screening or as diagnostic or
monitoring platform, the modern facility and the diverse
competencies at the institute comprise a strong partner
for assay adaptation and development.
The entire value chain is covered at the Fraunhofer IZI –
from the identication of the target molecule to validation
and, if appropriate, clinical testing of the assays.
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Nucleic Acid Based Assays
Protein Based Assays / Immunoassays
Cell Based Assays
Assay Development at Fraunhofer IZI
– tilling-array
– ELISA
– comet assay
Identication of Target Molecules
– high throughput sequencing
– immunoblot
– MTT assay
Identication of suitable target proteins and gene that
– transcriptome sequencing
– precipitation tests
– stem cell assay
demonstrate disease association
– RNA interference assay
– proteome analyses
– embryo toxicity assay
– promotor methylation assay
– serologic multiplex analyses
– cytotoxicity assays
Biomarker Development
– telomerase activity assay
– proliferation assay
Design and synthesis of probes with high afnity and
– gene expression analysis
– differentiation assay
specicity to a target
– mutation analyses
– caspase assay
– propidium iodide assay
Adaptation of Analytic Platforms
– FACS
Adaptation of existing (proteomic and genomic) technology platforms to the assay requirements
Parameter Optimization
Assay optimization with regard to specicity, sensitivity,
measuring speed and costs
Evaluation
Evaluation of the assay using patient samples in comparison to the gold-standard in the laboratory
Clinical Validation
Validation of the assay using patient samples in a clinical
framework
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FRAUNHOFER-GESELLSCHAFT
Aims and Principles
Structure
Alliances in the Fraunhofer-Gesellschaft
The Fraunhofer-Gesellschaft is one of Germany‘s big
The Fraunhofer-Gesellschaft maintains 57 institutes with
The Fraunhofer-Gesellschaft is divided into seven thematic
four research organizations. It is currently the largest
around 80 research units at more than 40 locations in
groups with separate ofces to coordinate their joint
European organization conducting applied research, the
Germany. The vast majority of the nearly 14,000 staff are
activities.
outcome of which has direct benets for business and
qualied scientists and engineers. They work with an
society. Its clients and contract partners include industrial
annual research budget of more than 1.4 billion euros,
– information and communication technology
companies, the service sector and the public sector. By
over 1.2 billion euros of which is generated through
– microelectronics
developing state-of-the-art technology on behalf of its
contract research. Roughly two thirds of the Fraunhofer-
– production
clients, the various Fraunhofer institutes help reinforce
Gesellschaft‘s research revenue stems from industry
– materials and components
the competitive strength of the economy in their local
contracts and publicly nanced research. The remainder is
– life sciences
region as well as throughout Germany and Europe. Ulti-
contributed by national and regional governments, partly
– surface technology and photonics
mately, the Fraunhofer-Gesellschaft aims to promote the
as a means of enabling the institutes to pursue funda-
– defense and security
development of a society that is economically successful
mental research in areas that are rst likely to become
without losing sight of social welfare or environmental
relevant to industry and society after ve or ten years.
responsibility. The Fraunhofer-Gesellschaft was founded
Afliated research centers and branches in Europe, the
in 1949 and is a recognized nonprot organization. Its
USA and Asia facilitate contact to the main regions of
members include prestigious companies and private
current and future scientic progress and economic
patrons, who help shape Fraunhofer‘s research policy and
development. As an employer, the Fraunhofer-Gesellschaft
strategic development. The organization was named after
offers its staff the opportunity to develop the professional
Joseph von Fraunhofer (1787–1826), an optician from
and personal skills they need to take up positions of
Munich, who became a successful researcher, inventor
responsibility within their institute, in other scientic
and entrepreneur.
domains and in business and society.
Josef von Fraunhofer (1787
bis 1826) – researcher, inven-
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tor, businessman.
Fraunhofer IZI Service Catalog | 23
PROFILE OF THE FRAUNHOFER IZI
Aims
In the face of an aging society and an increase in chronic
tissue, are expected to be available soon. In addition, a
Field of Research:
Field of Research:
prominent role is played by the development of immuno-
Immunology – Immunomodulation
Molecular Biology – Individualized Medicine
modulation techniques such as vaccination.
diseases, medicine is confronted with new challenges. The
This area includes the development of methods for
In the eld of molecular biology, Fraunhofer IZI is working
Fraunhofer Institute for Cell Therapy and Immunology IZI
In line with its four elds of research, Fraunhofer IZI
the stimulation or suppression of the immune system.
on a new technology platform which enables RNA mole-
has dened goals to embrace the promise of health and
is currently divided into 15 thematically clustered
One key topic is improving the smooth acceptance of
cules to be identied and ascertained for their potential
vitality even as the body ages.
groups. Fraunhofer IZI serves clients from the biotech-
transplants by inducing specic tolerance. Fraunhofer IZI
to effect the intracellular control of signal processes. This
nology industry, suppliers of medical equipment and
develops techniques to monitor immunoreactivity and to
provides indications for the development of new drugs.
In this aspect, the eld of regenerative medicine has
pharmaceutical companies by performing intelligent,
monitor unwanted responses such as GvHD (Graft versus
Furthermore, Fraunhofer IZI develops pharmacogenomic
become increasingly important for the health care system.
research-intensive services and carrying out development
Host Disease). It also develops vaccines on an innovative
and protein-chemistry techniques for the identication
This novel biomedical research area has the potential to
projects. The range of services offered by the institute
technology platform using plasmid DNA which are
of individual-specic differences from which particular
ght chronic diseases, autoimmune diseases and onco-
includes market analyses, technical feasibility studies,
particularly safe, robust and inexpensive.
disease susceptibility, sensitivity to certain methods of
logic diseases, which lead often to irreversible damage of
and prototype development using human and animal
tissue and organs. The goal is to use cell therapies, tissue
cells and tissues, as well as the conclusive formulation of
engineering or specic modulation of the immune system
production and process technologies.
to treat degenerative diseases based on root causes rather
therapy and even the course of disease can be predicted.
Field of Research:
Cell Therapy – Active Agents
History
Field of Research:
In this area, cells are developed, cultivated and bred for
The institute was ofcially founded in April 2005. Its rst
Biotechniques – Models
therapeutic purposes. Fraunhofer IZI offers isolation and
experimental work was conducted under a cooperation
than treating only the symptoms.
This goal can be reached through the stimulation of
purication methods for cells from blood and tissue. It
agreement with the University of Leipzig at the Max Bürger
In this area, Fraunhofer IZI develops technologies for the
also develops special treatment techniques using T-cell
Research Center, before being continued and extended
cultivation of tissues and cells outside the body (tissue
clones and natural killer cells as well as vaccination stra-
at Fraunhofer IZI‘s own laboratory at BIO CITY Leipzig
engineering) in order to reconstruct tissues. This includes
tegies using dendritic cells for tumor treatment. One key
in autumn 2005. This was only possible because 1,500
General Theme:
the development of custom bioreactors and the selection
area is cell therapy techniques for ischemic diseases such
square meters of laboratory and ofce space at BIO CITY
Cell Therapy and Immunology
of specic material and surface properties. Fraunhofer
as stroke and myocardial infarction. Ongoing projects
had been swiftly equipped thanks to smooth cooperation
naturally regenerative processes of the body or by biological replacements via extracorporally engineered tissue.
IZI also has special expertise in developing techniques
also include research into methods of preventing the
on the part of all those involved. In this context, it should
In its narrow sense, cell therapy means the transfer of cells
for the production of cell and tissue cultures as well as
degeneration and aging of cells. Furthermore, the
be underlined that a newly devised clean room facility
to replace lost functions and even to adopt additional
monoclonal antibodies. The institute’s in-house produc-
institute explores “dormant” stem cell potential and
for GMP work in cell and tissue technology was planned,
active tasks. It however also covers the treatment of cells
tion facilities are designed for the manufacture of clinical
derives new strategies for drugs able to control tissue
designed, built and validated within the space of just ten
through the repairing of deciencies. Stem cells can be
trial samples. Regarding the production of antibodies,
growth and regeneration.
months, entering into operation when the rst projects
transferred in order to trigger tissue formation and repair.
Fraunhofer IZI is also skilled in the downstream processing
were performed there in summer 2006. On September
Cell therapy is hence related to immunology, which
of raw products. Cell and tissue models developed by
22, 2006, the cornerstone for the institute was laid right
deals with cellular defense and monitoring mechanisms.
our researchers can be used for testing, screening and
next door to BIO CITY for a 4,000 square meter building,
Cell therapy techniques for the targeted strengthening,
the immunotoxicological examination of new drugs,
which since April 2008 has offered exceptional working
suppression and regeneration of the immune system, for
cosmetics, food additives and industrial chemicals. The
conditions.
example in order to stimulate the defense of degenerated
institute offers various small- and large-animal models for
cells or to suppress the undesired rejection of transplanted
therapy development along the stages of the pharmaceutical development value chain.
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Management
Structure
Animal Experiments
The structure and operation of Fraunhofer IZI are based
In its current phase of development, Fraunhofer IZI is
The rst extension wing of the institute will include a
on the successful experience of other Fraunhofer Institutes
divided into 15 (increased to 17 in 2009) groups managed
department devoted to animal experiments. Experiments
gathered over the years. The director of our institute is
by their group leaders as business units. Their budgets are
on animals are currently carried out in cooperation
Prof. Dr. Frank Emmrich, who is also a professor at the
negotiated with the management of the institute every
with the Faculty of Veterinary Medicine, the Faculty of
University of Leipzig, where he has headed the Institute
year – and the development and funding of each group
Medicine and the Max Planck Institute for Evolutionary
of Clinical Immunology and Transfusion Medicine since
largely depend on their success in attracting projects
Anthropology. In addition, projects involving animal
1994. This dual position enables the efcient sharing of
and contracts. Individual groups develop particular
experiments have begun with the Faculty of Biology,
experience, not to mention the optimal supervision of
competencies which are made available as services not
Pharmacy and Psychology.
undergraduate and doctoral dissertations, and provides
just externally, but also internally. The varied research
an excellent basis for cooperation. Both a doctor and an
competencies and services lead to synergies inside the
immunologist, Prof. Emmrich spent 13 years as both a
institute and offer new perspectives to customers and
researcher and department head at Max Planck Institutes
research partners.
in Freiburg and Erlangen. Over seven of these years he
One outstanding achievement in terms of precision and
was a professor at the Friedrich Alexander University in
Erlangen-Nuremberg.
GMP Facility
speed is the planning and completion of Fraunhofer
Facilities
IZI‘s multi-purpose GMP facility at the BIO CITY. It was
planned, built and approved within the space of just ten
On the premises and in laboratory space currently used,
months, enabling the rst major contract to be started in
Fraunhofer IZI maintains standard laboratory facilities for
summer 2006. It was also ensured that the new building
biochemistry, molecular biology and cell biology, including
would be connected via a bridge so that the GMP facility
The head of the institute is assisted by Patric Nitz – an
a large inventory of equipment which is augmented by
can continue to be used – hence granting planning
administrator with an academic background in both
systems and instruments that are used cooperatively.
certainty to all the partners involved.
management and the organization of staff training.
For further details, please see the descriptions of the
He also holds an MBA from a British university and has
individual groups.
Administration
several years experience managing departments and
divisions in large organizational units in the public and
private sectors.
26 | Fraunhofer IZI Service Catalog
Fraunhofer IZI Service Catalog | 27
Leipzig
8
9
2 7b
6
7c
4
11
RESEARCH ENVIRONMENT LEIPZIG
A9
7a
1
3
10
5
B2
A38
1
Translational Centre for Regenerative Medicine
3
Center for Biotechnology and Biomedicine (BBZ)
5
Heart Centre
Translational Center for
(TRM)
Regenerative Medicine (1),
In the framework of the Biotechnology Initiative of the
The Heart Centre Leipzig GmbH – University Hospital is a specialty hospital that houses
Interdisciplinary Center for
In 2006, the Translational Centre for Regenerative Medi-
Free State of Saxony, ve faculties joined together to
cardiac surgery, internal medicine, cardiology, pediatrics and child cardiology. With 330
Clinical Research (2), Fraun-
cine was founded in Leipzig and installed in immediate
create a key project to be established in the BIO CITY
beds and 10 day-clinic places, the Heart Centre provides top-notch medical treatment for
hofer Institute for Cell
proximity to the BIO CITY and Fraunhofer IZI. The TRM is
Leipzig: thus the Center for Biotechnology and Biomedi-
all aspects of the heart. In addition the clinical resources, research is a major activity at
Therapy and Immunology (3),
a part of the excellence grants from the Federal Ministry
cine was founded. The Free State of Saxony granted 200
the Heart Centre, in particular in the areas of developing new operative techniques and
Centre for Biotechnology and
cardiovascular basic research.
Biomedicine (3), University
of Education and Research and the Free State of Saxony.
million euros to establish the BIO CITY, including the BBZ.
Institutes from across ve faculties are integrated into the
Particular support for Fraunhofer IZI is expected from the
TRM which is directed by Prof. Emmrich. Together they
BBZ Members in the areas of Cell Techniques and Applied
established four research areas: Tissue Engineering and
Stem Cell Biology, Bio-process Technology, Protein Struc-
Materials Science (TEMAT), Cell Therapies for Repair and
ture Analysis, Mass Spectroscopy, Molecular Cell Therapy
Replacement (CELLT), Regulatory Molecules and Delivery
and Molecular Pathogenesis.
Hospital (4), Heart Center (5),
Coordination Center for
6
Coordination Center for Clinical Trials (KKSL)
Clinical Trials (6), Interdisciplinary Center for Bioinformatics
Innovative structures for clinical research (i. e. planning and performing clinical trials) have
(6), Interdisciplinary Trans-
Systems (REMOD) and Imaging, Modelling, and Monito-
become very successfully established in Leipzig. The Federal Ministry of Education and
genesis Center (3), Max Planck
ring of Regeneration (IMONIT). Conceptional, preclinical
Research provided funding for the Coordination Center for Clinical Trials Leipzig (KKSL)
Institute for Evolutionary
where trial assistants and doctors can be trained and clinical studies devised. In addition,
Anthropology (7a), Max
Innomed Leipzig GmbH’s Center for Therapy Studies (ZET) is an organization that carries
Planck Institute for Mathe-
and clinical research projects are supported by the TRM.
Clinical Competence – Transplantation
The initial grant for the institution is 20 million euros
over four years. The Free State of Saxony is providing
Leipzig’s clinical prole is characterized by particular
out clinical trials with doctors treating outpatients. Both institutions already work very
matics in the Sciences (7b),
an additional 17 million euros for building renovations
expertise in the elds of cell and tissue transplantation.
closely with Fraunhofer IZI.
Max Planck Institut for Cog-
and basic equipment. As well as playing a key role in the
For example, heart and lung transplants are carried out
application to establish TRM, Fraunhofer IZI also maintains
at the Heart Centre Leipzig, while the University Hospital
diverse links with the TRM.
specializes in liver, kidney and pancreas transplants. In
nitive and Brain Sciences (7c),
Helmholtz Centre for Environ6
Interdisciplinary Center for Bioinformatics (IZBI)
mental Research (8), Leibniz
addition, the José Carreras Foundation has opened a
2
Interdisciplinary Centre for Clinical Research
(IZKF)
bone marrow transplant center, while the German Organ
Thanks to nancial support from the German Research Foundation (DFG), Leipzig has
tion (8), Association for the
Donation Foundation (DSO) has set up a logistics center
established an Interdisciplinary Center for Bioinformatics (IZBI). Its main tasks are the
Advancement of the Health
for tissue conservation.
modelling of mechanisms of cellular signal transduction and data processing for cell
Economics of the Region Leip-
analysis techniques. In particular, Fraunhofer IZI’s RNomics Group cooperates intensively
zig (3), University of Leipzig
with IZBI.
(9), University of Applied
The Interdisciplinary Centre for Clinical Research Leipzig
was founded in 1996 as a center of excellence of the
Institute of Surface Modica-
4
University Hospital
Science (10), Graduate School
Federal Ministry of Education and Research at the Faculty
of Management (11)
of Medicine to initially focus on cell-cell and cell-matrix
The University Hospital is associated with one of the
3
Interdisciplinary Transgenesis Center
interactions of diagnostic and therapeutic signicance.
oldest medical training locations in Germany. Research fo-
Scientic focuses are on immunology, endocrinology,
cuses of the hospital include neurodegenerative diseases
The Faculty of Veterinary Medicine, Faculty of Medicine and the Max Planck Institute for
neurosciences and oncology. The centre also maintains
such as Alzheimer’s disease, Parkinson’s and retinal
Evolutionary Anthropology joined forces to found a transgenesis center where pionee-
various junior groups and the service units specializing in
degeneration, immunological questions on immune
ring techniques for the introduction and elimination of genes can be developed – for
DNA sequencing and peptide technology.
reactivity, immunological tolerance as well as projects in
instance in connection with the development of new pathogenetic models in animals.
molecular oncology.
28 | Fraunhofer IZI Service Catalog
Fraunhofer IZI Service Catalog | 29
V
IV
Zw
er
au
ick
Deutscher
Platz
RESEARCH CONTRACTS
ße
ra
St
III
ra
ße
I
II
P
VI
Pe
rli
ck
st
Ia
P
BIO CITY (I) with hired Fraun-
7a 7b 7c
Max Planck Institutes (MPIs)
The institutes of the Fraunhofer-Gesellschaft view
Phase 1 – Condentiality Agreement
themselves as professional research service providers.
Signing of a non-disclosure agreement.
Veterinary Medicine, insti-
Cooperation with the three Max Planck Institutes in Leipzig is only natural. The Max
They render their service on the basis of contracts that
Original text may be from the partner or
tutes and hospitals (II), Max
Planck Institute for Human Congnitive and Brain Sciences (7c) provides special expertise
dene the content and deadlines as prescribed by the
Fraunhofer-Gesellschaft.
Planck Institute for Evolutio-
for modern imaging technologies and very valuable facilities are accessible, such as,
clients and that also reect client’s own needs and
nary Anthropology (III), Ger-
for example, MRI. The MPI for Mathematics in the Sciences (7b) is the sponsor of the
specications. Of course, in the rst phase, clients may
man National Library (IV),
IZBI, in addition to the university. The cooperation between the MPI for Evolutionary
be assured of condentiality and non-disclosure of
Translational Centre for
Anthropology (MPI-EVA) (7a) (Prof. S. Pääbo) is especially interesting and has yielded
the contracted project.
Regenerative Medicine (V),
internationally recognized research in molecular and developmental biology.
hofer IZI area (Ia), Faculty of
new building of Fraunhofer
Fraunhofer IZI has standardized contracts for phase 1,
IZI (VI).
but is also prepared to make use of partner or client con8
Helmholtz Centre for Environmental Research – UFZ
Phase 2 – Term Sheet
Denition of the cornerstones between the
partners (IP rights, utilization rights, contract timeframe, project plan, nancial development).
tracts that have been legally reviewed by the FraunhoferGesellschaft. The contacts for this phase and in following
The Helmholtz Centre for Environmental Research – UFZ is a member of the Helmholtz-
phases of partnership are the members of the Project
Gesellschaft and one of the German government’s biggest research institutions. Many
Service Team (PST) and / or the group leaders in whose
working groups there represent great technological experience with bioreactors for
eld the agreed research services will occur.
microbiolgy, sensor technology and cell culture.
Phase 3 – Offer
Drafting of the contract based on the project plan
In phase 2, the cornerstones of a contract are dened
and cornerstones as dened in phase 2.
in a term sheet by the partner institutions. To effectively
8
Leibniz Institute for Surface Modication (IOM)
plan the targets, the contract timeframe and nancial
development are also sketched at this phase. The views
The IOM carries out application oriented basic research with the goal of transferring
of both parties regarding IP rights and utilization options
their results into new technologies. Their focus is on examining the interactions between
will be agreed in essential points.
radiation and materials. Knowledge of physical and chemical processes support the
Phase 4 – Contract negotiation
development and production of insulating, metallic, semiconducting and polymer
On this basis, the staff of Fraunhofer IZI prepares an offer
Discussion and nalization of the contract
surfaces.
or draft contract that will be discussed and negotiated in
by the partners.
phase 4.
3
Association for the Advancement of the Health Economics of the Region
Leipzig (VGF)
After review by the legal advisors of the partners, the
agreement of the contract and its signing follows in
phase 5.
This association, founded in 2004, has the mission to promote the region of Leipzig as
Phase 5 – Contract agreement
a leading center for medical science and practice in Germany and internationally. The
Signing of the research contract after review and,
group is composed of researchers, doctors, clinics, practices, laboratories and commercial
if necessary, changes by the legal advisors of the
partners. Contacts in the VGF are primarily scientists, industry members, interest groups,
partners.
doctors, patients and the interested public.
30 | Fraunhofer IZI Service Catalog
Fraunhofer IZI Service Catalog | 31
CONTACT
Immunological Models
Extracorporeal Immune
Tumor Stem Cells
Prof. Dr. Frank Emmrich
Dr. Manja Kamprad
Modulation
Dr. Peter Ruschpler
Phone +49 (0) 341 / 355 36-9105
Phone +49 (0) 341 / 97 25-830
Prof. Dr. Steffen Mitzner
Phone +49 (0) 341 / 355 36-2605
frank.emmrich@
manja.kamprad@
Phone +49 (0) 381 / 494 73 53
peter.ruschpler@
izi.fraunhofer.de
izi.fraunhofer.de
steffen.mitzner@
izi.fraunhofer.de
Director
izi.fraunhofer.de
Bio Nanober Scaffolds
Dr. Gyeong-Man Kim
Administrative Head
Patric Nitz
Phone +49 (0) 341 / 355 36-1400
Phone +49 (0) 341 / 355 36-9200
[email protected]
[email protected]
Immunology – Immunomodulation
Molecular Biology – Individualized Medicine
Cell Therapy – Active Agents
Vascular Biology
Immunotherapy – Oncology
Dr. Andreas Schubert
Dr. Christoph Schimmelpfennig
Phone +49 (0) 341 / 355 36-5105
Phone +49 (0) 341 / 355 36-3105
andreas.schubert@
christoph.schimmelpfennig@
izi.fraunhofer.de
izi.fraunhofer.de
Project Service Team
Dr. Wilhelm Gerdes
Vaccine Development
Phone +49 (0) 341 / 355 36-9300
Dr. Sebastian Ulbert (Laboratory)
Neurorepair
Dr. Jörg Hackermüller
wilhelm.gerdes@
PD Dr. Matthias Giese
Dr. Johannes Boltze
Phone +49 (0) 341 / 355 36-5205
izi.fraunhofer.de
(Head of Group)
Phone +49 (0) 341 / 97 25-820
joerg.hackermueller@
Phone +49 (0) 341 / 355 36-2106
johannes.boltze@
izi.fraunhofer.de
[email protected]
izi.fraunhofer.de
Immune Tolerance
Stem Cell Technology
Prof. Dr. Ulrich Sack
RNomics
Molecular Diagnostics
Biotechniques – Models
Dr. Stephan Fricke
Prof. Dr. Nicole zur Nieden
Phone +49 (0) 341 / 97 25-506
Cell Engineering / GMP
Phone +49 (0) 341 / 355 36-2205
Phone +49 (0) 341 / 355 36-3305
[email protected]
Dr. Gerno Schmiedeknecht
stephan.fricke@
nicole.zurnieden@
Phone +49 (0) 341 / 355 36-9705
izi.fraunhofer.de
izi.fraunhofer.de
Virus-Host-Interaction
Stem Cell Biology
gerno.schmiedeknecht@
izi.fraunhofer.de
Dr. Jörg Baumann
Dr. Alexandra Stolzing
Cell Engineering / GLP
Phone +49 (0) 341 / 355 36-2505
Phone +49 (0) 341 / 355 36-3405
Dr. Jörg Lehmann
[email protected]
alexandra.stolzing@
Phone +49 (0) 341 / 355 36-1205
Dr. Sabine Breun
izi.fraunhofer.de
joerg.lehmann@
Phone +49 (0) 341 / 355 36-2506
izi.fraunhofer.de
[email protected]
32 | Fraunhofer IZI Service Catalog
Fraunhofer IZI Service Catalog | 33
HOW TO REACH US
Fraunhofer Institute for
Stö
Cell Therapy and Immunology
itze
r St
stra
ße
tter
raß
e
eck
Perlickstr. 1
Rieb
04103 Leipzig
Germany
Russische
Ph
s1
se
nt
ha
8.
O
er
ob
kt
www.izi.fraunhofer.de
H
e
aß
de
[email protected]
kirche
Ro
lstr
ße
p-
Semmelweisstraße
l-S
Da
tra
uth
ge
ra
Fax: +49 (0) 341 / 355 36-9921
ße
est
Kre
ilip
St
Phone: +49 (0) 341 / 355 36-1000
Gedächtnis-
raß
e
Deutsche
lw
me
Sem
right onto Perlickstraße.
Tierklink
tra
nT
ße
de
Augustusplatz (Leipzig Opera House). At Augustusplatz
str
allee). After the central railway station turnright towards
rS
into Zwickauer Straße heading for ”Alte Messe”. Turn
ge
follow the B87 (Merseburger Straße, Lützner Str., Jahn-
Platz
UniPra
Lehmann-Straße and exit before the BMW car show room
An
Take the B181 heading for the city center (”Zentrum”),
intersection turn right into Puschstraße. At the end of the
Transport
n
ike
Reaching Fraunhofer IZI by Train and Public
klin
Straße. Turn right onto ”Alte Messe” and after the second
ier
turn left and keep to the right, afterwards follow Prager
road turn left into Perlickstraße.
Fraunhofer IZI
H
Travel to Leipzig Central Station (”Leipziger Hauptbahn-
16
Zwickauer Straße
From the Airport
left onto Prager Straße (B2) heading for ”Alte Messe”.
Then turn right onto ”Alte Messe” and after the second
Take the train to Leipzig Central Station (”Leipziger
intersection turn right into Puschstraße. At the end of the
Hauptbahnhof”). Then continue by tram (see above).
nho
Messegelände
off the tram at ”An den Tierkliniken”.
Take the B2 (via Maximilianallee) heading for the city
center (”Zentrum”), follow B2 (via Gerichtsweg). Turn
Nau
Altes
hof”), take the number 16 tram heading for Lößnig, get
A14 – Exit Leipzig-Mitte
e
Deutscher
turn off into Richard-Lehmann-Straße. Follow Richard-
aß
Take the B2 heading for the city center (”Zentrum”),
ntz
A9 – Exit Leipzig-West
Bücherei
e
raß
t
eiss
Gü
38 – Exit Leipzig-Süd
St
ferst
raße
ra
ße
de
s1
8.
road turn left into Perlickstraße.
Friedhofsweg
Reaching Fraunhofer IZI by Car
Ok
to
be
r
B2
aksmühle
An der Tab
Richard-Lehmann-
Straße
34 | Fraunhofer IZI Service Catalog
Fraunhofer-Institut für
Zelltherapie und Immunologie
Perlickstr. 1
04103 Leipzig
Germany
Phone: +49 (0) 341 / 355 36-1000
Fax: +49 (0) 341 / 355 36-9921
[email protected]
www.izi.fraunhofer.de
© Fraunhofer IZI, Stand: 04/2009
Bone and Cartilage Failures
Immunology
– Cartilage Destruction Model in the Mouse ........IZI530-02
– Cellular Function Test for Tissue-destructive
Fibroblasts ........................................................IZI530-03
– Proof of Biocompatibility and Risk Analysis........IZI130-01
– Therapy Model for Tissue Regeneration
(Fractures).........................................................IZI330-01
– Three-dimensional Stem Cell Cultures Bone /
Cartilage – Mechanical Training ........................IZI330-02
– Antigen Specic Tolerance Induction .................IZI250-01
– Conditioned Humanized / Non Humanized
Mouse Model ...................................................IZI220-01
– Customized Development and Validation
of Immunological In Vitro Test Systems .............IZI120-04
– Dendritic Cells and Cytokine Induced
Killer Cells ........................................................IZI310-04
– GvHD-Model in Mice ........................................IZI220-03
– Humanized, Triple Transgenic Mouse ................IZI220-02
– Proof of Biocompatibility and Risk Analysis........IZI130-01
– Therapeutic Mouse Model: A Human
Immune System for Testing of Active
Ingredients .......................................................IZI130-02
Cardiology
– Animal Model Systems for Cardiac
Ischemia – Rat / Mouse ......................................IZI320-07
Infectious Diseases
Haematology
– Conditioned Humanized / Non Humanized
Mouse Model ...................................................IZI220-01
– Dendritic Cells and Cytokine Induced
Killer Cells ........................................................IZI310-04
– micro RNA Analysis (Expression, Localization,
Targets) ............................................................IZI520-05
– Therapeutic Mouse Model: A Human
Immune System for Testing of Active
Ingredients .......................................................IZI130-02
– Highly Complex cDNA Libraries .........................IZI250-02
– Defensins and Antimicrobial Peptides................IZI510-01
– Diagnosis and Therapy Model (Mouse)
of Borreliosis (Borrelia burgdorferi) ....................IZI120-08
– Diagnosis and Therapy Model (Mouse)
of Salmonellosis (Salmonella enterica) ...............IZI120-07
– Microarray Analysis ...........................................IZI520-06
– Non-coding RNAs as Therapeutic Targets ..........IZI520-03
– Screening for Compounds with
Antiviral Activity ...............................................IZI250-03
– Nanometer Pathogen-Sieb ................................IZI250-04
Immune Mediated Diseases
– Antigen Specic Tolerance Induction .................IZI250-01
– Therapy Models (Mouse) of Chronicinammatory Bowel Diseases ............................IZI120-06
F r a u n h o f e r I Z I S e r v i c e C a t a l o g | Ta b l e o f C o n t e n t s
INDICATIONS
TABLE OF CONTENTS –
INDICATIONS
Inammatory Diseases
Transplantation Medicine
–
–
–
–
–
– Antigen Specic Tolerance Induction .................IZI250-01
– Conditioned Humanized / Non Humanized
Mouse Model ...................................................IZI220-01
– GvHD-Model in Mice ........................................IZI220-03
– Optimization Cell and Tissue
Cryoconservation ..............................................IZI340-01
Arthritis Model in the Mouse ............................IZI530-01
Cartilage Destruction Model in the Mouse ........IZI530-02
Cell Tracking .....................................................IZI310-02
Cell Transduction ..............................................IZI250-05
Cellular Function Test for Tissue-destructive
Fibroblasts ........................................................IZI530-03
– Histology of the Mammalian Brain ....................IZI320-05
– Therapy Models (Mouse) of Chronicinammatory Bowel Diseases ............................IZI120-06
Metabolism
Vascular Biology
– Assay System for Isolation of Biomarkers in
Arteriosclerosis / Dental Plaque ..........................IZI510-02
– Cell Tracking .....................................................IZI310-02
Neurology
–
–
–
–
–
–
–
Cell Culture Models ..........................................IZI320-01
Experimental Imaging .......................................IZI320-04
Histology of the Mammalian Brain ....................IZI320-05
Microarray Analysis ...........................................IZI520-06
Non-coding RNAs as Therapeutic Targets ..........IZI520-03
Ovine Large Animal Model of Stroke.................IZI320-03
Rat Model of Focal Cerebral Ischemia
(Stroke).............................................................IZI320-02
Oncology
–
–
–
–
–
–
–
–
–
–
–
–
Antigen Specic Tolerance Induction .................IZI250-01
Cell Tracking .....................................................IZI310-02
Cell Transduction ..............................................IZI250-05
Cytostatic Drugs and Cell Therapeutic
Drugs Screening Assays / In Vivo Testing in
Mouse Model Following Tumor Induction .........IZI360-03
Cytostatic Drugs / In Vitro Testing of
Tumor Stem Cells for Various Solid
Malignant Tumors.............................................IZI360-01
Highly Complex cDNA Libraries .........................IZI250-02
Histology of the Mammalian Brain ....................IZI320-05
Microarray Analysis ...........................................IZI520-06
micro RNA Analysis (Expression, Localization,
Targets) ............................................................IZI520-05
Non-coding RNA Biomarkers for
Oncological Diseases, nONCOchip ....................IZI520-02
Non-coding RNAs as Therapeutic Targets ..........IZI520-03
Personalized Tumor Killer-Cells ..........................IZI360-02
F r a u n h o f e r I Z I S e r v i c e C a t a l o g | Ta b l e o f C o n t e n t s
TABLE OF CONTENTS –
COMPETENCIES
– Animal Model Systems for Cardiac
Ischemia – Rat / Mouse ......................................IZI320-07
– Arthritis Model in the Mouse ............................IZI530-01
– Assay System for Isolation of Biomarkers in
Arteriosclerosis / Dental Plaque ..........................IZI510-02
– Cartilage Destruction Model in the Mouse ........IZI530-02
– Cell Culture Models ..........................................IZI320-01
– Cellular Function Test for Tissue-destructive
Fibroblasts ........................................................IZI530-03
– Cytostatic Drugs and Cell Therapeutic
Drugs Screening Assays / In Vivo Testing in
Mouse Model Following Tumor Induction .........IZI360-03
– Cytostatic Drugs / In Vitro Testing of
Tumor Stem Cells for Various Solid
Malignant Tumors.............................................IZI360-01
– Defensins and Antimicrobial Peptides................IZI510-01
– Developmental Toxicity of Additives,
Compounds, Supplements and Biomaterials .....IZI330-04
– Diagnosis and Therapy Model (Mouse)
of Borreliosis (Borrelia burgdorferi) ....................IZI120-08
– Diagnosis and Therapy Model (Mouse)
of Salmonellosis (Salmonella enterica) ...............IZI120-07
– GLP Studies – Differential Proteomics
(Available 2009)................................................IZI120-09
– GLP Studies – Immunotoxicology (In Vitro)
(Available 2009)................................................IZI120-10
– GvHD-Model in Mice ........................................IZI220-03
– micro RNA Analysis (Expression, Localization,
Targets) ............................................................IZI520-05
– Ovine Large Animal Model of Stroke.................IZI320-03
– Personalized Tumor Killer-Cells ..........................IZI360-02
– Rat Model of Focal Cerebral Ischemia
(Stroke).............................................................IZI320-02
– Screening for Compounds with
Antiviral Activity ...............................................IZI250-03
– (Stem Cell) Cytotoxicity of Additives,
Compounds, Supplements and Biomaterials .....IZI330-05
– Therapeutic Mouse Model: A Human
Immune System for Testing of Active
Ingredients .......................................................IZI130-02
– Therapy Models (Mouse) of Chronicinammatory Bowel Diseases ............................IZI120-06
– Three-dimensional Stem Cell Cultures Bone /
Cartilage – Mechanical Training ........................IZI330-02
Analytics
– Microarray Analysis ...........................................IZI520-06
– micro RNA Analysis (Expression, Localization,
Targets) ............................................................IZI520-05
Antibody Development and Testing
– Arthritis Model in the Mouse ............................IZI530-01
– Cartilage Destruction Model in the Mouse ........IZI530-02
– Cellular Function Test for Tissue-destructive
Fibroblasts ........................................................IZI530-03
– Conjugation of Antibodies – Generation ...........IZI120-03
– Humanized, Triple Transgenic Mouse ................IZI220-02
– Monoclonal Antibodies – Generation ................IZI120-01
– Polyclonal Antibodies – Generation ...................IZI120-02
– GMP Manufacturing of Monoclonal
Antibodies ........................................................IZI110-02
Biocompatibility Studies
– Proof of Biocompatibility and Risk Analysis........IZI130-01
– (Stem Cell) Cytotoxicity of Additives,
Compounds, Supplements and Biomaterials .....IZI330-05
– Therapy Model for Tissue Regeneration
(Fractures).........................................................IZI330-01
F r a u n h o f e r I Z I S e r v i c e C a t a l o g | Ta b l e o f C o n t e n t s
COMPETENCIES
Active Agents and Drug Delivery (Testing /
Development)
Cell Therapeutics
GLP
– Animal Model Systems for Cardiac
– Conjugation of Antibodies – Generation ...........IZI120-03
– Customized Development and Validation
of Immunological In Vitro Test Systems .............IZI120-04
– Diagnosis and Therapy Model (Mouse)
of Borreliosis (Borrelia burgdorferi) ....................IZI120-08
– Diagnosis and Therapy Model (Mouse)
of Salmonellosis (Salmonella enterica) ...............IZI120-07
– GLP Studies – Differential Proteomics
(Available 2009)................................................IZI120-09
– GLP Studies – Immunotoxicology (In Vitro)
(Available 2009)................................................IZI120-10
– Monoclonal Antibodies – Generation ................IZI120-01
– Polyclonal Antibodies – Generation ...................IZI120-02
– Therapy Models (Mouse) of Chronicinammatory Bowel Diseases ............................IZI120-06
– Validation and Beta-evaluation of Celltechnological Procedures / Instruments ..............IZI120-05
–
–
–
–
–
Ischemia – Rat / Mouse ......................................IZI320-07
Antigen Specic Tolerance Induction .................IZI250-01
Cell Culture Models ..........................................IZI320-01
Ovine Large Animal Model of Stroke.................IZI320-03
Rat Model of Focal Cerebral Ischemia
(Stroke).............................................................IZI320-02
Therapeutic Mouse Model: A Human
Immune System for Testing of Active
Ingredients .......................................................IZI130-02
Cell Therapy
– Dendritic Cells and Cytokine Induced
Killer Cells ........................................................IZI310-04
Clinical Trials
GMP
– Bioluminescence and Fluorescence Imaging
for Preclinical In Vivo Small Animal Studies........IZI310-01
– Dendritic Cells and Cytokine Induced
Killer Cells ........................................................IZI310-04
– Non-coding RNA Biomarkers ............................IZI520-01
– Non-coding RNA Biomarkers for
Oncological Diseases, nONCOchip ....................IZI520-02
– GMP Manufacturing of Cell Based Medicinal
Products and Tissue Preparations ......................IZI110-01
– GMP Manufacturing of Monoclonal
Antibodies ........................................................IZI110-02
Material and Surface Testing
– Animal Model Systems for Cardiac
Diagnostics and Monitoring
– Bioluminescence and Fluorescence Imaging
for Preclinical In Vivo Small Animal Studies........IZI310-01
– Cell Transduction ..............................................IZI250-05
– Conjugation of Antibodies – Generation ...........IZI120-03
– Experimental Imaging .......................................IZI320-04
– micro RNA Analysis (Expression, Localization,
Targets) ............................................................IZI520-05
– Monoclonal Antibodies – Generation ................IZI120-01
– Non-coding RNA Biomarkers ............................IZI520-01
– Non-coding RNA Biomarkers for
Oncological Diseases, nONCOchip ....................IZI520-02
– Non-coding RNAs as Therapeutic Targets ..........IZI520-03
– Polyclonal Antibodies – Generation ...................IZI120-02
– SNP Analysis in Human Genome .......................IZI320-06
– Transcriptome Analysis Using Tiling Arrays
and Ultra-high-throughput Sequencing.............IZI520-04
– Nanometer Pathogen-Sieb ................................IZI250-04
Ischemia – Rat / Mouse ......................................IZI320-07
– Proof of Biocompatibility and Risk Analysis........IZI130-01
– (Stem Cell) Cytotoxicity of Additives,
Compounds, Supplements and Biomaterials .....IZI330-05
– Therapy Model for Tissue Regeneration
(Fractures).........................................................IZI330-01
Tissue Engineering
– GMP Manufacturing of Cell Based Medicinal
Products and Tissue Preparations ......................IZI110-01
– Optimization Cell and Tissue
Cryoconservation ..............................................IZI340-01
– Proof of Biocompatibility and Risk Analysis........IZI130-01
F r a u n h o f e r I Z I S e r v i c e C a t a l o g | Ta b l e o f C o n t e n t s
Cell Techniques
Model Systems
–
–
–
–
Antigen Specic Tolerance Induction .................IZI250-01
Cell Culture Models ..........................................IZI320-01
Cell Transduction ..............................................IZI250-05
Cellular Function Test for Tissue-destructive
Fibroblasts ........................................................IZI530-03
– Dendritic Cells and Cytokine Induced
Killer Cells ........................................................IZI310-04
– Non-coding RNA Biomarkers for
Oncological Diseases, nONCOchip ....................IZI520-02
– Validation and Beta-evaluation of Celltechnological Procedures / Instruments ..............IZI120-05
– Animal Model Systems for Cardiac
Cryoconservation
–
– Optimization Cell and Tissue
Cryoconservation ..............................................IZI340-01
–
–
–
–
–
–
–
–
–
Imaging
–
– Bioluminescence and Fluorescence Imaging
for Preclinical In Vivo Small Animal Studies........IZI310-01
– Cell Tracking .....................................................IZI310-02
– Experimental Imaging .......................................IZI320-04
–
–
–
–
–
Immune Techniques
–
– Proof of Biocompatibility and Risk Analysis........IZI130-01
– Therapeutic Mouse Model: A Human
Immune System for Testing of Active
Ingredients .......................................................IZI130-02
–
–
Microbiology
–
– Defensins and Antimicrobial Peptides................IZI510-01
–
Ischemia – Rat / Mouse ......................................IZI320-07
Arthritis Model in the Mouse ...........................IZI530-01
Assay System for Isolation of Biomarkers in
Arteriosclerosis / Dental Plaque ..........................IZI510-02
Cartilage Destruction Model in the Mouse .......IZI530-02
Cell Culture Models ..........................................IZI320-01
Cell Tracking .....................................................IZI310-02
Conditioned Humanized / Non Humanized
Mouse Model ...................................................IZI220-01
Cytostatic Drugs and Cell Therapeutic
Drugs Screening Assays / In Vivo Testing in
Mouse Model Following Tumor Induction .........IZI360-03
Cytostatic Drugs / In Vitro Testing of
Tumor Stem Cells for Various Solid
Malignant Tumors.............................................IZI360-01
Developmental Toxicity of Additives,
Compounds, Supplements and Biomaterials .....IZI330-04
Diagnosis and Therapy Model (Mouse)
of Borreliosis (Borrelia burgdorferi) ....................IZI120-08
Diagnosis and Therapy Model (Mouse)
of Salmonellosis (Salmonella enterica) ...............IZI120-07
GvHD-Model in Mice ........................................IZI220-03
Humanized, Triple Transgenic Mouse ................IZI220-02
Ovine Large Animal Model of Stroke.................IZI320-03
Personalized Tumor Killer-Cells ..........................IZI360-02
Rat Model of Focal Cerebral Ischemia
(Stroke).............................................................IZI320-02
(Stem Cell) Cytotoxicity of Additives,
Compounds, Supplements and Biomaterials .....IZI330-05
Therapeutic Mouse Model: A Human
Immune System for Testing of Active
Ingredients .......................................................IZI130-02
Therapy Model for Tissue Regeneration
(Fractures).........................................................IZI330-01
Therapy Models (Mouse) of Chronicinammatory Bowel Diseases ............................IZI120-06
Three-dimensional Stem Cell Cultures Bone /
Cartilage – Mechanical Training ........................IZI330-02
F r a u n h o f e r I Z I S e r v i c e C a t a l o g | Ta b l e o f C o n t e n t s
TECHNOLOGIES
TABLE OF CONTENTS –
TECHNOLOGIES
Molecular Biology
Proteomics
– Assay System for Isolation of Biomarkers in
Arteriosclerosis / Dental Plaque ..........................IZI510-02
– Cell Transduction ..............................................IZI250-05
– Highly Complex cDNA Libraries .........................IZI250-02
– Defensins and Antimicrobial Peptides................IZI510-01
– Microarray Analysis ...........................................IZI520-06
– micro RNA Analysis (Expression, Localization,
Targets) ............................................................IZI520-05
– Non-coding RNA Biomarkers ............................IZI520-01
– Non-coding RNA Biomarkers for
Oncological Diseases, nONCOchip ....................IZI520-02
– Non-coding RNAs as Therapeutic Targets ..........IZI520-03
– Screening for Compounds with
Antiviral Activity ...............................................IZI250-03
– SNP Analysis in Human Genome .......................IZI320-06
– Transcriptome Analysis Using Tiling Arrays
and Ultra-high-throughput Sequencing.............IZI520-04
– Nanometer Pathogen-Sieb ................................IZI250-04
– GLP Studies – Differential Proteomics
(Available 2009)................................................IZI120-09
Process Development
– Cell Transduction ..............................................IZI250-05
– Conjugation of Antibodies – Generation ...........IZI120-03
– Customized Development and Validation
of Immunological In Vitro Test Systems .............IZI120-04
– GMP Manufacturing of Cell Based Medicinal
Products and Tissue Preparations ......................IZI110-01
– Monoclonal Antibodies – Generation ................IZI120-01
– Polyclonal Antibodies – Generation ...................IZI120-02
– Screening for Compounds with
Antiviral Activity ...............................................IZI250-03
– Validation and Beta-evaluation of Celltechnological Procedures / Instruments ..............IZI120-05
– Nanometer Pathogen-Sieb ................................IZI250-04
– GMP Manufacturing of Monoclonal
Antibodies ........................................................IZI110-02
Stem Cell Technology
– Cell Culture Models ..........................................IZI320-01
– Cell Transduction ..............................................IZI250-05
– Cytostatic Drugs and Cell Therapeutic
Drugs Screening Assays / In Vivo Testing in
Mouse Model Following Tumor Induction .........IZI360-03
– Cytostatic Drugs / In Vitro Testing of
Tumor Stem Cells for Various Solid
Malignant Tumors.............................................IZI360-01
– Developmental Toxicity of Additives,
Compounds, Supplements and Biomaterials .....IZI330-04
– GMP Manufacturing of Cell Based Medicinal
Products and Tissue Preparations ......................IZI110-01
– Non-coding RNA Biomarkers ............................IZI520-01
– Ovine Large Animal Model of Stroke.................IZI320-03
– Personalized Tumor Killer-Cells ..........................IZI360-02
– Proof of Biocompatibility and Risk Analysis........IZI130-01
– Rat Model of Focal Cerebral Ischemia
(Stroke).............................................................IZI320-02
– Reprogramming of Cells – iPS
(induced Pluripotent Stem Cells) .......................IZI340-02
– Screening for Anti-aging and Regeneration
Substances .......................................................IZI340-03
– (Stem Cell) Cytotoxicity of Additives,
Compounds, Supplements and Biomaterials .....IZI330-05
– Stem Cell Media Formulations ..........................IZI330-03
– Therapeutic Mouse Model: A Human
Immune System for Testing of Active
Ingredients .......................................................IZI130-02
– Three-dimensional Stem Cell Cultures Bone /
Cartilage – Mechanical Training ........................IZI330-02
F r a u n h o f e r I Z I S e r v i c e C a t a l o g | Ta b l e o f C o n t e n t s
TABLE OF CONTENTS –
GROUPS
Cell Engineering / GLP
Immune Tolerance
– Conjugation of Antibodies – Generation ...........IZI120-03
– Customized Development and Validation
of Immunological In Vitro Test Systems .............IZI120-04
– Diagnosis and Therapy Model (Mouse)
of Borreliosis (Borrelia burgdorferi) ....................IZI120-08
– Diagnosis and Therapy Model (Mouse)
of Salmonellosis (Salmonella enterica) ...............IZI120-07
– GLP Studies – Differential Proteomics
(Available 2009)................................................IZI120-09
– GLP Studies – Immunotoxicology (In Vitro)
(Available 2009)................................................IZI120-10
– Monoclonal Antibodies – Generation ................IZI120-01
– Polyclonal Antibodies – Generation ...................IZI120-02
– Therapy Models (Mouse) of Chronicinammatory Bowel Diseases ............................IZI120-06
– Validation and Beta-evaluation of Celltechnological Procedures / Instruments ..............IZI120-05
– Conditioned Humanized / Non Humanized
Mouse Model ...................................................IZI220-01
– GvHD-Model in Mice ........................................IZI220-03
– Humanized, Triple Transgenic Mouse ................IZI220-02
Cell Engineering / GMP
– GMP Manufacturing of Cell Based Medicinal
Products and Tissue Preparations ......................IZI110-01
– GMP Manufacturing of Monoclonal
Antibodies ........................................................IZI110-02
Immunological Models
– Proof of Biocompatibility and Risk Analysis........IZI130-01
– Therapeutic Mouse Model: A Human
Immune System for Testing of Active
Ingredients .......................................................IZI130-02
Immunotherapy – Oncology
– Bioluminescence and Fluorescence Imaging
for Preclinical In Vivo Small Animal Studies........IZI310-01
– Cell Tracking .....................................................IZI310-02
– Clean Room Cell Sorting ...................................IZI310-03
– Dendritic Cells and Cytokine Induced
Killer Cells ........................................................IZI310-04
Molecular Diagnostics
GROUPS
– Arthritis Model in the Mouse ............................IZI530-01
– Cartilage Destruction Model in the Mouse ........IZI530-02
– Cellular Function Test for Tissue-destructive
Fibroblasts ........................................................IZI530-03
F r a u n h o f e r I Z I S e r v i c e C a t a l o g | Ta b l e o f C o n t e n t s
Neurorepair
Tumor Stem Cells
– Animal Model Systems for Cardiac
– Cytostatic Drugs and Cell Therapeutic
Drugs Screening Assays / In Vivo Testing in
Mouse Model Following Tumor Induction .........IZI360-03
– Cytostatic Drugs / In Vitro Testing of
Tumor Stem Cells for Various Solid
Malignant Tumors.............................................IZI360-01
– Personalized Tumor Killer-Cells ..........................IZI360-02
–
–
–
–
–
–
Ischemia – Rat / Mouse ......................................IZI320-07
Cell Culture Models ..........................................IZI320-01
Experimental Imaging .......................................IZI320-04
Histology of the Mammalian Brain ....................IZI320-05
Ovine Large Animal Model of Stroke.................IZI320-03
Rat Model of Focal Cerebral Ischemia
(Stroke).............................................................IZI320-02
SNP Analysis in Human Genome .......................IZI320-06
Vascular Biology
RNomics
– Microarray Analysis ...........................................IZI520-06
– micro RNA Analysis (Expression, Localization,
Targets) ............................................................IZI520-05
– Non-coding RNA Biomarkers ............................IZI520-01
– Non-coding RNA Biomarkers for
Oncological Diseases, nONCOchip ....................IZI520-02
– Non-coding RNAs as Therapeutic Targets ..........IZI520-03
– Transcriptome Analysis Using Tiling Arrays
and Ultra-high-throughput Sequencing.............IZI520-04
– Assay System for Isolation of Biomarkers in
Arteriosclerosis / Dental Plaque ..........................IZI510-02
– Defensins and Antimicrobial Peptides................IZI510-01
Virus-Host-Interaction
–
–
–
–
Antigen Specic Tolerance Induction .................IZI250-01
Cell Transduction ..............................................IZI250-05
Highly Complex cDNA Libraries .........................IZI250-02
Screening for Compounds with
Antiviral Activity ...............................................IZI250-03
– Nanometer Pathogen-Sieb ................................IZI250-04
Stem Cell Biology
– Optimization Cell and Tissue
Cryoconservation ..............................................IZI340-01
– Reprogramming of Cells – iPS
(induced Pluripotent Stem Cells) .......................IZI340-02
– Screening for Anti-aging and Regeneration
Substances .......................................................IZI340-03
Stem Cell Technology
– Developmental Toxicity of Additives,
Compounds, Supplements and Biomaterials .....IZI330-04
– (Stem Cell) Cytotoxicity of Additives,
Compounds, Supplements and Biomaterials .....IZI330-05
– Stem Cell Media Formulations ..........................IZI330-03
– Therapy Model for Tissue Regeneration
(Fractures).........................................................IZI330-01
– Three-dimensional Stem Cell Cultures Bone /
Cartilage – Mechanical Training ........................IZI330-02
F r a u n h o f e r I Z I S e r v i c e C a t a l o g | Ta b l e o f C o n t e n t s
FRAUNHOFER INSTITUTE FOR CELL THERAPY AND IMMUNOLOGY
GMP MANUFACTURING OF CELL
BASED MEDICINAL PRODUCTS AND
TISSUE PREPARATIONS
Prole of the Fraunhofer IZI
Cell Engineering / GMP Group
The Fraunhofer Institute for Immunology and Cell Therapy
We operate a modern clean room facility for manufacturing in-
IZI founded in April 2005 is member of the Fraunhofer
vestigational medicinal products according to Good Manufacturing
Life Sciences Alliance. Its objective being to nd solutions
Practice (GMP). Our expertise is primarily in the areas of cell
to specic problems at the interfaces between medicine,
based therapeutics (e.g., tissue engineered products), therapeutic
life sciences and engineering for partners active in
recombinant glycoproteins and antibodies. Our services span
medicine-related industries and businesses. The Institute’s
all phases from process development to the manufacturing of
core competencies are to be found in regenerative
investigational new products.
medicine, or more precisely in cell-therapeutic methods of
regenerating non-functioning tissue and organs through
to the biological substitution with tissue cultivated in vitro
(tissue engineering). In order for the living organism to
accept the tissues without any difculty, it is necessary
to study cellular and immunological defense and control
mechanisms and take these into account during process
and product development. These core competencies
entail a multiplicity of tasks to be solved by new products
and processes. The Institute works especially closely with
hospital institutions, performing quality tests and clinical
studies on their behalf. Additionally it also provides
assistance in obtaining manufacturing licenses and
certications.
Fraunhofer-Institut für
Zelltherapie und Immunologie
Contact
Director
Dr. Gerno Schmiedeknecht
Prof. Dr. Frank Emmrich
Cell Engineering / GMP Group
Perlickstr. 1
Phone: +49 (0) 341 / 355 36-9705
04103 Leipzig
[email protected]
Germany
Phone:
+49 (0) 341 / 355 36-1000
Fax :
+49 (0) 341 / 355 36-9921
[email protected]
PN: IZI110-01
www.izi.fraunhofer.de
© Fraunhofer IZI, status: 04/2009
GMP MANUFACTURING OF CELL
BASED MEDICINAL PRODUCTS AND
TISSUE PREPARATIONS
Clinical trials using advanced medicinal products require
Unique Feature
Selected Applications
Associated Products & Services at the Institute
factured according to European Good Manufacturing
The partition of the facility into different suites helps avoid
Providing investigational medicinal products for clinical trials
–
Cell Culture Models (IZI320-01)
Practice (GMP), the “Guideline on human cell based
campaign production, something that, in practice with
with advanced medicinal products (tissue engineered
–
Cell Tracking (IZI310-02)
medicinal products” of the European Medicinal
tissue engineering products, can only be achieved with
products, somatic cell therapy medicinal products, gene
–
Clean Room Cell Sorting (IZI310-03)
Agency (EMEA), the German Drug Law (AMG) and the
difculty due to week long production processes. As a
therapy medicinal products) in order to obtain a central
–
Dendritic Cells and Cytokine Induced Killer Cells
German Ordinance for the Production of Medicinal
consequence the individual cell product of each customer
authorization by the EMEA according to regulation (EC)
Products and Active Substances (AMWHV). Therefore,
can be provided continuously. The exible design of the
no. 1394 / 2007.
Fraunhofer IZI provides a highly qualied interdisciplinary
facility and the comprehensive technical equipment with-
team, a comprehensive quality assurance system, a
out any specialization to a specic product enables the
pharmaceutical clean room facility that adheres to the
manufacture and quality control of different autologous
newest technical and regulatory standards and last, but
and allogenic medicinal products (tissue engineered
not least, a well equipped quality control laboratory. Of
products, stem cell therapeutics, cancer vaccines, gene
Manufacturing EpiDex™ “autologous skin from hair
particular interest, is the separation of the entire facility
therapeutics). So it will be possible to full nearly each
roots” together with the Leipzig based biotech company
into several independent clean room suites, which enables
customer requirement in the eld of advanced medicinal
euroderm GmbH.
the establishment of several specic production processes
products.
high quality investigational medicinal products manu-
(IZI310-04)
–
Optimization Cell and Tissue Cryoconservation
(IZI340-01)
–
Reprogramming of Cells – iPS (induced Pluripotent
Stem Cells) (IZI340-02)
Reference Project
–
Therapy Model for Tissue Regeneration (Fractures)
(IZI330-01)
–
Three-dimensional Stem Cell Cultures Bone / Cartilage –
Mechanical Training (IZI330-02)
–
for individual products in parallel and independent from
Validation and Beta-evaluation of Cell-technological
Procedures / Instruments (IZI120-05)
other ongoing processes, as well the individual application
for a manufacturing authorization according to § 13
Technical Data
Further Products & Services of this Group
AMG. This partition helps to minimise the risk of cross
contaminations between the different manufacturing
The facility with a total area of 450 m2 is mainly designed
processes. The existing qualied GMP compliant technical
for the sterile manufacturing of cell based medicinal
equipment and the qualications of the staff allow the
products and tissue preparations. This is reected by a
application of a broad and modern spectrum of methods
high amount (64 percent) of class B (ISO 5, class 100)
for the isolation, cultivation, cryopreservation and storage
clean room areas. Class A (ISO 4.8, class 100) clean room
of human cells. Besides the manufacturing and quality
conditions for work on open cell and tissue products are
control of cell based medicinal products and tissue prepa-
guaranteed through laminar ow units that are integrated
rations by Fraunhofer IZI staff, the clean rooms themselves
in all class B clean room manufacturing rooms. A cascade
can be used by customers in order to obtain their own
of airlocks starting from class D (ISO 8, class 100 000)
manufacturing authorization according to §13 AMG with
clean rooms allows a GMP-compliant entry and exit of
all associated privileges and responsibilities.
the facility with a strict separation of material and staff
–
GMP Manufacturing of Monoclonal Antibodies
(IZI110-02)
transfer. All critical parameters like air-borne particles,
room pressure, laminar airow, temperature, moisture
and the correct function of important technical devices
are permanently monitored and recorded by a 21 CFR
part 11-compliant software solution.
Fraunhofer IZI Service Catalog | IZI110-01
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Prof. Dr. Frank Emmrich
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Perlickstr. 1
Phone: +49 (0) 341 / 355 36-1205
04103 Leipzig
[email protected]
Germany
Phone:
+49 (0) 341 / 355 36-1000
Fax :
+49 (0) 341 / 355 36-9921
[email protected]
PN: IZI120-01
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IZI founded in April 2005 is member of the Fraunhofer
for immunotoxicological studies (in vitro and in vivo) and differen-
(EMEA ICH S8) and chemicals (REACH). Another main focus of
life sciences and engineering for partners active in
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medicine-related industries and businesses. The Institute’s
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core competencies are to be found in regenerative
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biochemical methodology.
regenerating non-functioning tissue and organs through
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to study cellular and immunological defense and control
mechanisms and take these into account during process
and product development. These core competencies
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Director
Dr. Joerg Lehmann
Prof. Dr. Frank Emmrich
Cell Engineering / GLP Group
Perlickstr. 1
Phone: +49 (0) 341 / 355 36-1205
04103 Leipzig
[email protected]
Germany
Phone:
+49 (0) 341 / 355 36-1000
Fax :
+49 (0) 341 / 355 36-9921
[email protected]
PN: IZI120-02
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Monoclonal Antibodies – Generation (IZI120-01)
therapeutic purposes
–
Conjugation of Antibodies – Generation (IZI120-03)
Quality Management System.
–
Customized Development and Validation of Immuno-
One of the special competences of the Fraunhofer IZI is
development and generation of customized polyclonal
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IZI founded in April 2005 is member of the Fraunhofer
for immunotoxicological studies (in vitro and in vivo) and differen-
(EMEA ICH S8) and chemicals (REACH). Another main focus of
life sciences and engineering for partners active in
"
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04103 Leipzig
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Perlickstr. 1
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04103 Leipzig
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Germany
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Perlickstr. 1
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04103 Leipzig
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Germany
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–
GLP Studies – Immunotoxicology (In Vitro)
(Available 2009) (IZI120-10)
$VVRFLDWHG3URGXFWV6HUYLFHVDWWKH,QVWLWXWH
–
Animal Model Systems for Cardiac Ischemia –
Rat / Mouse (IZI320-07)
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(IZI520-05)
–
SNP Analysis in Human Genome (IZI320-06)
–
Transcriptome Analysis Using Tiling Arrays and
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)5$81+2)(5,167,787()25&(//7+(5$3<$1',00812/2*<
GLP STUDIES – IMMUNOTOXICOLOGY
(IN VITRO) (AVAILABLE 2009)
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The Fraunhofer Institute for Immunology and Cell Therapy
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IZI founded in April 2005 is member of the Fraunhofer
for immunotoxicological studies (in vitro and in vivo) and differen-
(EMEA ICH S8) and chemicals (REACH). Another main focus of
life sciences and engineering for partners active in
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medicine-related industries and businesses. The Institute’s
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core competencies are to be found in regenerative
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biochemical methodology.
regenerating non-functioning tissue and organs through
in vitro
(tissue engineering). In order for the living organism to
to study cellular and immunological defense and control
mechanisms and take these into account during process
and product development. These core competencies
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studies on their behalf. Additionally it also provides
assistance in obtaining manufacturing licenses and
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Director
Dr. Joerg Lehmann
Prof. Dr. Frank Emmrich
Cell Engineering / GLP Group
Perlickstr. 1
Phone: +49 (0) 341 / 355 36-1205
04103 Leipzig
[email protected]
Germany
Phone:
+49 (0) 341 / 355 36-1000
Fax :
+49 (0) 341 / 355 36-9921
[email protected]
PN: IZI120-10
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© Fraunhofer IZI, status: 04/2009
GLP STUDIES – IMMUNOTOXICOLOGY
(IN VITRO) (AVAILABLE 2009)
6HOHFWHG$SSOLFDWLRQV
6SHFLDO1RWH
)XUWKHU3URGXFWV6HUYLFHVRIWKLV*URXS
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All offered services of the Cell Engineering / GLP Group
–
Monoclonal Antibodies – Generation (IZI120-01)
$\
–
Polyclonal Antibodies – Generation (IZI120-02)
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=^<^?Y‰
involved in innate or adaptive immunity.
Quality Management System.
–
Conjugation of Antibodies – Generation (IZI120-03)
–
Customized Development and Validation of Immuno-
The Fraunhofer IZI is currently establishing a broad-range
in vitro test battery for immunotoxicology studies under
]^?Y>Y
logical In Vitro Test Systems (IZI120-04)
tendency to avoid animal experiments for this purpose.
Y
5HIHUHQFH3URMHFW
–
Validation and Beta-evaluation of Cell-technological
Procedures / Instruments (IZI120-05)
in vitro test systems. The Fraunhofer IZI is in that
QUUŠ\
Study of effects of different phytopharmaceuticals on the
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function of certain immune cells in vitro.
K&
=NOQU!UW>
–
Diagnosis and Therapy Model (Mouse) of Salmonellosis
tion. Although national or international authorities expect
(Salmonella enterica) (IZI120-07)
a complete immunotoxicology study under GLP conditions
\
–
For this reason the previously established immunotoxico-
Diagnosis and Therapy Model (Mouse) of Borreliosis
(Borrelia burgdorferi) (IZI120-08)
rather performed under GLP-analogous conditions.
–
GLP Studies – Differential Proteomics (Available 2009)
(IZI120-09)
logical methods may be used in F&E-contract research
'*
$VVRFLDWHG3URGXFWV6HUYLFHVDWWKH,QVWLWXWH
; &#\
?
Supplements and Biomaterials (IZI330-04)
–
Proof of Biocompatibility and Risk Analysis (IZI130-01)
–
Screening for Anti-aging and Regeneration Substances
(IZI340-03)
)UDXQKRIHU,=,6HUYLFH&DWDORJ_,=,
FRAUNHOFER INSTITUTE FOR CELL THERAPY AND IMMUNOLOGY
PROOF OF BIOCOMPATIBILITY
AND RISK ANALYSIS
Prole of the Fraunhofer IZI
Immunological Models Group
The Fraunhofer Institute for Immunology and Cell Therapy
This group is focused on the isolation, cultivation and the
IZI founded in April 2005 is member of the Fraunhofer
phenotypical and functional characterization of mesenchymal and
Life Sciences Alliance. Its objective being to nd solutions
hematopoietic stem cells for the development of regenerative
to specic problems at the interfaces between medicine,
therapies. Based on the formation of functional human immuno-
life sciences and engineering for partners active in
competent cells in a mouse model, the development of disease
medicine-related industries and businesses. The Institute’s
models and therapy processes are being pursued in cooperation
core competencies are to be found in regenerative
with the University of Leipzig.
medicine, or more precisely in cell-therapeutic methods of
regenerating non-functioning tissue and organs through
to the biological substitution with tissue cultivated in vitro
(tissue engineering). In order for the living organism to
accept the tissues without any difculty, it is necessary
to study cellular and immunological defense and control
mechanisms and take these into account during process
and product development. These core competencies
entail a multiplicity of tasks to be solved by new products
and processes. The Institute works especially closely with
hospital institutions, performing quality tests and clinical
studies on their behalf. Additionally it also provides
assistance in obtaining manufacturing licenses and
certications.
Fraunhofer-Institut für
Zelltherapie und Immunologie
Contact
Director
Dr. Manja Kamprad
Prof. Dr. Frank Emmrich
Immunological Models Group
Perlickstr. 1
Phone: +49 (0) 341 / 97 25-830
04103 Leipzig
[email protected]
Germany
Phone:
+49 (0) 341 / 355 36-1000
Fax :
+49 (0) 341 / 355 36-9921
[email protected]
PN: IZI130-01
www.izi.fraunhofer.de
© Fraunhofer IZI, status: 04/2009
PROOF OF BIOCOMPATIBILITY
AND RISK ANALYSIS
Bone tissue replacement is necessary for treatment of
Methods
Erythrocytes
large bone defects. Implantations of scaffolds, which
induce an endogenous repair, are able to solve this
Mesenchymal stem cells
problem. Such osteoinductive materials support migration
–
and proliferation of mesenchymal stem cells, and their
differentiation into osteocytes.
–
–
haemolysis
–
aggregation
Further Products & Services of this Group
–
for Testing of Active Ingredients (IZI130-02)
in vitro culture of human mesenchymal stem cells
from bone marrow with material under static culture
Phagocytes
condition
–
phagocytosis
in vitro culture of human mesenchymal stem cells
–
respiratory burst
Depending on the size and location of the bone defect
from bone marrow with material under differentiation
which is also related to blood supply and mechanical con-
conditions (osteogenic, adipogenic, chondrogenic
ditions, different materials (permanent or biodegradable)
differentiation)
Selected Applications
Associated Products & Services at the Institute
–
Antigen Specic Tolerance Induction (IZI250-01)
–
Bioluminescence and Fluorescence Imaging for
Preclinical In Vivo Small Animal Studies (IZI310-01)
are needed to regenerate the bone. The development
of new biomedical scaffold materials (processing,
Mesenchymal stem cells / lymphocytes
functionalized surface) is addressed to improve adhesion,
–
proliferation / cytotoxicity assay
proliferation and differentiation of mesenchymal stem
–
adhesion assay
cells and to minimize immunological adverse effect.
–
cell cycle analysis (static, dynamic)
–
apoptosis / necrosis assay
–
analysis of immunosuppressive property of
Therefore, we focus of the establishment of a widespread
Therapeutic Mouse Model: A Human Immune System
biologic risk analysis system at an early-stage of material
–
proof of new designed materials or functionalized
–
Cartilage Destruction Model in the Mouse (IZI530-02)
surface of materials with osteoinductive / osteo-
–
Cellular Function Test for Tissue-destructive Fibroblasts
(IZI530-03)
conductive properties (tissue engineering)
–
risk analysis of compounds / materials (stem cell toxicity,
–
(Available 2009) (IZI120-10)
immunotoxicity)
–
mesenchymal stem cells
design, which accelerates the progression of basic mate-
–
secretion of cytokine, growth factor, chemokines
rial science into pre-clinical and clinical application.
–
phenotypical analysis
–
comet assay
GLP Studies – Immunotoxicology (In Vitro)
risk analysis of compounds / materials (erythrocytes,
–
GvHD-Model in Mice (IZI220-03)
thrombocytes, phagocytes)
–
Therapy Model for Tissue Regeneration (Fractures)
(IZI330-01)
–
Reference Project
Three-dimensional Stem Cell Cultures Bone / Cartilage –
Mechanical Training (IZI330-02)
Our extended in vitro risk analysis system includes stem
cells assays as well as immunological assays (T and B
Thrombocytes
An open-pored biodegradable material with osteoinductive
cells, phagocytes), detection of thrombolytic / thrombolic
–
activation
properties was characterized by in vitro immunological
and hematolytic activity, evaluation of platelet adhesion
–
aggregation
assays. We could show that the scaffold did not induce
and platelet activation, genotoxic and carcinogenic risk
activation / proliferation of T and B cells, and of thrombo-
analysis.
cytes.
material testing and risk analysis, biocompatibility
adult stem cells
peripheral blood cells
hematopoietic
mesenchymal
lymphocytes
phagocytes
stem cells (cord
stem cells (bone
(T and B cells)
(monocytes,
blood)
marrow)
thrombocytes
erythrocytes
granulocytes)
Fraunhofer IZI Service Catalog | IZI130-01
FRAUNHOFER INSTITUTE FOR CELL THERAPY AND IMMUNOLOGY
THERAPEUTIC MOUSE MODEL:
A HUMAN IMMUNE SYSTEM FOR
TESTING OF ACTIVE INGREDIENTS
Prole of the Fraunhofer IZI
Immunological Models Group
The Fraunhofer Institute for Immunology and Cell Therapy
This group is focused on the isolation, cultivation and the
IZI founded in April 2005 is member of the Fraunhofer
phenotypical and functional characterization of mesenchymal and
Life Sciences Alliance. Its objective being to nd solutions
hematopoietic stem cells for the development of regenerative
to specic problems at the interfaces between medicine,
therapies. Based on the formation of functional human immuno-
life sciences and engineering for partners active in
competent cells in a mouse model, the development of disease
medicine-related industries and businesses. The Institute’s
models and therapy processes are being pursued in cooperation
core competencies are to be found in regenerative
with the University of Leipzig.
medicine, or more precisely in cell-therapeutic methods of
regenerating non-functioning tissue and organs through
to the biological substitution with tissue cultivated in vitro
(tissue engineering). In order for the living organism to
accept the tissues without any difculty, it is necessary
to study cellular and immunological defense and control
mechanisms and take these into account during process
and product development. These core competencies
entail a multiplicity of tasks to be solved by new products
and processes. The Institute works especially closely with
hospital institutions, performing quality tests and clinical
studies on their behalf. Additionally it also provides
assistance in obtaining manufacturing licenses and
certications.
Fraunhofer-Institut für
Zelltherapie und Immunologie
Contact
Director
Dr. Manja Kamprad
Prof. Dr. Frank Emmrich
Immunological Models Group
Perlickstr. 1
Phone: +49 (0) 341 / 97 25-830
04103 Leipzig
[email protected]
Germany
Phone:
+49 (0) 341 / 355 36-1000
Fax :
+49 (0) 341 / 355 36-9921
[email protected]
PN: IZI130-02
www.izi.fraunhofer.de
© Fraunhofer IZI, status: 04/2009
THERAPEUTIC MOUSE MODEL:
A HUMAN IMMUNE SYSTEM FOR
TESTING OF ACTIVE INGREDIENTS
Unique Feature
Reference Project
Further Products & Services of this Group
ADME, toxicology and new chemical, pharmaceutical or
The human cell population is stably expressed for over
Patients with severe systemic immune reaction show
–
biopharmaceutical substances.
6 months which allows long-lasting studies with new
increased serum concentrations of immunological in-
potential agents under in vivo conditions in this unique
ammation parameters (interleukin 6, interleukin 8, tumor
Recently, we developed a humanized mouse model,
mouse model. Prodrugs converted in the liver to an active
necrosis factor alpha). Humanized mice display reaction
which is characterized by stable and long-term engraft-
form can also be investigated in this mouse model.
patterns comparable with this clinical situation. All engraft-
Humanized mice with a functional humane immune
system present a suitable model for in vivo studies of
ment of human immunocompetent cells (patent).
Following the transfer of mononuclear cord blood cells
(IZI130-01)
Associated Products & Services at the Institute
ed animals showed increased concentration of human
Methods
in conditioned NOD / SCID mice, all animals reconstituted
long-lasting human haematopoiesis. Human multilineage
Proof of Biocompatibility and Risk Analysis
interleukin 6 and interleukin 8. Additionally, animals secrete
–
Arthritis Model in the Mouse (IZI530-01)
human interleukin-1 beta, interleukin-10, interleukin-12p70
–
Assay System for Isolation of Biomarkers in
Arteriosclerosis / Dental Plaque (IZI510-02)
and tumor necrosis factor in different patterns. Synthetic
–
differentiation of blood cells, can be observed in blood,
reconstitution of human immune cells in immuno-
glucocorticoid prednisone (immunosuppressive, anti-
decient mouse
inammatory agent) modulates human cytokine secretion.
–
Bioluminescence and Fluorescence Imaging for
Preclinical In Vivo Small Animal Studies (IZI310-01)
spleen and bone marrow, and the generated cells
–
application of agents (i.v., i.p., s.c.)
–
Cell Culture Models (IZI320-01)
include B cells, T helper cells, cytotoxic T cells, NK cells,
–
ow cytometric analysis of human and murine cells
–
Cell Tracking (IZI310-02)
(peripheral blood, bone marrow, spleen)
–
Conditioned Humanized / Non Humanized Mouse
monocytes, dendritic cells, granulocytes and CD34+
haematopoietic stem cells. All animals produce human
–
immunoglobulins. Functional analyses of human cells
chemokine) and antibodies in body uids
reveal that B cells undergo normal class switching and
–
produce T-cell-dependent antigen-specic immuno-
–
globulins. Human cells secreted pro-inammatory
Model (IZI220-01)
quantication of human mediators (cytokine,
–
in vitro culture of single cell suspension or isolated
Cytostatic Drugs / In Vitro Testing of Tumor Stem Cells
for Various Solid Malignant Tumors (IZI360-01)
human / murine cell isolation using magnetic beads
–
Developmental Toxicity of Additives, Compounds,
Supplements and Biomaterials (IZI330-04)
cells, phenotyping of cultured cells, function test
cytokines (interleukin-1 beta, interleukin-6, tumor necrosis
–
Humanized, Triple Transgenic Mouse (IZI220-02)
factor alpha) in response to acute inammation using
–
Rat Model of Focal Cerebral Ischemia (Stroke)
LPS application. Using ow-cytometric analysis human
–
In vivo material testing with human cells in murine
The patent xeno-transplantation protocol was established
(IZI320-02)
Selected Applications
plasmocytoid and myeloid dendritic cells were detectable.
Screening for Anti-aging and Regeneration Substances
(IZI340-03)
background
by our group at the University of Leipzig. Future models
can be developed in cooperation with Fraunhofer IZI.
Fraunhofer IZI Service Catalog | IZI130-02
FRAUNHOFER INSTITUTE FOR CELL THERAPY AND IMMUNOLOGY
CONDITIONED HUMANIZED /
NON HUMANIZED MOUSE MODEL
Prole of the Fraunhofer IZI
Immune Tolerance Group
The Fraunhofer Institute for Immunology and Cell Therapy
The goal of this group is the development of cell- and antibody-
IZI founded in April 2005 is member of the Fraunhofer
based therapeutic strategies to treat complications following
Life Sciences Alliance. Its objective being to nd solutions
hematopoietic stem cell transplantation. Novel concepts of
to specic problems at the interfaces between medicine,
immunological tolerance oriented towards immunologic and
life sciences and engineering for partners active in
therapy associated complications (e.g. GVHD) are being tested in
medicine-related industries and businesses. The Institute’s
new, in-house developed animal models.
core competencies are to be found in regenerative
medicine, or more precisely in cell-therapeutic methods of
regenerating non-functioning tissue and organs through
to the biological substitution with tissue cultivated in vitro
(tissue engineering). In order for the living organism to
accept the tissues without any difculty, it is necessary
to study cellular and immunological defense and control
mechanisms and take these into account during process
and product development. These core competencies
entail a multiplicity of tasks to be solved by new products
and processes. The Institute works especially closely with
hospital institutions, performing quality tests and clinical
studies on their behalf. Additionally it also provides
assistance in obtaining manufacturing licenses and
certications.
Fraunhofer-Institut für
Zelltherapie und Immunologie
Contact
Director
Dr. Stephan Fricke
Prof. Dr. Frank Emmrich
Immune Tolerance Group
Perlickstr. 1
Phone: +49 (0) 341 / 355 36-2205
04103 Leipzig
[email protected]
Germany
Phone:
+49 (0) 341 / 355 36-1000
Fax :
+49 (0) 341 / 355 36-9921
[email protected]
PN: IZI220-01
www.izi.fraunhofer.de
© Fraunhofer IZI, status: 04/2009
CONDITIONED HUMANIZED /
NON HUMANIZED MOUSE MODEL
Methods
Reference Project
Further Products & Services of this Group
modulatory agents, there is a need for suitable models.
Following chemotherapy and / or irradiation, cells are
Using humanized mice, the therapeutic inuence of novel
–
Humanized, Triple Transgenic Mouse (IZI220-02)
The model offered here is composed of either humanized
transplanted into conditioned mice. For diagnosis of
stem cell fractions on the reconstitution of hematopoiesis
–
GvHD-Model in Mice (IZI220-03)
or wild-type mice undergoing conditioning by chemo-
therapeutic success clinical scores, peripheral blood
and their reparative abilities in different tissues and organs
therapy and / or irradiation followed by transplantation
parameters, ow cytometric analysis, histological /
could be investigated in detail. It could be shown that
of the stem cell- and organ fraction to be tested. The
immunohistochemical and molecular biological methods
a subset of murine stem cells provide an advantage
therapeutic follow-up is evaluated.
can be used. In addition cells can be specically marked to
compared to conventional cell therapeutics. Based on our
visualize them through immunouorescence microscopy
model, effects of conditioning and therapeutic activities
or bioluminescence imaging.
of different stem cell fractions could be described using
In order to assess the therapeutic efciency of solid
organ and cell suspension transplants as well as immuno-
According to the scientic question posed, stem cell or
organ fractions to be tested are transplanted into special-
hematologic parameters.
ized humanized or wild type mice after chemotherapy
and / or irradiation. Following application of the cells the
Associated Products & Services at the Institute
–
Preclinical In Vivo Small Animal Studies (IZI310-01)
–
Cell Transduction (IZI250-05)
–
Cellular Function Test for Tissue-destructive Fibroblasts
(IZI530-03)
Selected Applications
–
therapeutic efciency is assessed. This method resembles
procedures of organ or haematopoietic stem cell trans-
With the help of established procedures for condition-
plantation (HSCT) in humans.
ing, extensive stem cell- and organ transplantation
experiments can be performed in humanized and wild
Bioluminescence and Fluorescence Imaging for
(Stem Cell) Cytotoxicity of Additives, Compounds,
Supplements and Biomaterials (IZI330-05)
–
Therapeutic Mouse Model: A Human Immune System
for Testing of Active Ingredients (IZI130-02)
type mice. Biologic activity of these transplants can be
Unique Feature
tested in vivo. In particular the impact of stem cells on
hematopoiesis and their ability to repair tissue / organs can
The model of humanized mice allows unique analysis of
be depicted.
chimerism and provides a clear distinction between transplant and host even although donor and host organism
exhibit nearly identical antigenic properties.
Fraunhofer IZI Service Catalog | IZI220-01
FRAUNHOFER INSTITUTE FOR CELL THERAPY AND IMMUNOLOGY
HUMANIZED, TRIPLE TRANSGENIC
MOUSE
Prole of the Fraunhofer IZI
Immune Tolerance Group
The Fraunhofer Institute for Immunology and Cell Therapy
The goal of this group is the development of cell- and antibody-
IZI founded in April 2005 is member of the Fraunhofer
based therapeutic strategies to treat complications following
Life Sciences Alliance. Its objective being to nd solutions
hematopoietic stem cell transplantation. Novel concepts of
to specic problems at the interfaces between medicine,
immunological tolerance oriented towards immunologic and
life sciences and engineering for partners active in
therapy associated complications (e.g. GVHD) are being tested in
medicine-related industries and businesses. The Institute’s
new, in-house developed animal models.
core competencies are to be found in regenerative
medicine, or more precisely in cell-therapeutic methods of
regenerating non-functioning tissue and organs through
to the biological substitution with tissue cultivated in vitro
(tissue engineering). In order for the living organism to
accept the tissues without any difculty, it is necessary
to study cellular and immunological defense and control
mechanisms and take these into account during process
and product development. These core competencies
entail a multiplicity of tasks to be solved by new products
and processes. The Institute works especially closely with
hospital institutions, performing quality tests and clinical
studies on their behalf. Additionally it also provides
assistance in obtaining manufacturing licenses and
certications.
Fraunhofer-Institut für
Zelltherapie und Immunologie
Contact
Director
Dr. Stephan Fricke
Prof. Dr. Frank Emmrich
Immune Tolerance Group
Perlickstr. 1
Phone: +49 (0) 341 / 355 36-2205
04103 Leipzig
[email protected]
Germany
Phone:
+49 (0) 341 / 355 36-1000
Fax :
+49 (0) 341 / 355 36-9921
[email protected]
PN: IZI220-02
www.izi.fraunhofer.de
© Fraunhofer IZI, status: 04/2009
APC
HUMANIZED, TRIPLE TRANSGENIC
MOUSE
D1
D2
D3
D4
human HC-II
hHLA-DR
E2
D2
E1
D1
H
D
E
H J V
[
TCR/CD3
human CD4
mouse CD3
Functional analyses with monoclonal antibodies (mAb)
TH cell
Methods
Reference Project
vitro effects cannot completely be transferred to the in
Following application of antibodies a variety of analyses
Tolerance towards tetanus toxoid was achieved in human-
vivo situation. The triple transgenic mouse model (on a
can be carried out including analysis of optimal dose,
ized mice following anti-human CD4 treatment (Laub R et
stable C57Bl/6 genetic background) expresses human
potential of T cell depletion, detailed ow cytometric
al., Transplant Proc 2001; 33 (3): 2182-2183). Antibody
Right: Histological cross-
CD4- and MHC-II-molecules while murine CD4-molecules
analysis of lymphocyte subpopulations with or without
conditioning protocols have been established at Fraunhofer
section of skin following trans-
are knocked out (are not expressed). Thus it is possible
antigen-specic stimulation and studies of pharmaco-
IZI and transplantation experiments with TTG mice have
plantation of human PBMCs in
to directly test anti-human CD4 and anti-human MHC-II
kinetics using ELISA. In addition, peripheral blood para-
been carried out.
TTG mice. Detection of CD3+
antibodies in vivo. At the same time the interaction of the
meters, histological / immunohistochemical and molecular
complete accessory T cell synapses is simulated and can
biological methods can be used.
Left: Description of the animal
against human surface molecules in vivo are limited. In
model – phenotype (schematic)
be inuenced by anti-human CD4 and MHC-II antibodies.
of TTG mice.
human T cells in the skin.
In vitro studies in MLC-cultures demonstrate the therapeutic efciency of applied monoclonal antibodies. CD4
mAb are produced in the institute and can be used for the
Selected Applications
experiments.
Further Products & Services of this Group
Using humanized, triple transgenic, mice newly developed
The animals for the model are bred in cooperation with the
–
This triple transgenic mouse model is singular in this form
anti-human CD4 and anti-human MHC class II antibodies
University of Leipzig (Translational Centre for Regenerative
and allows investigation of anti-human CD4 and MHC-II
can directly be analyzed in vivo. In this way immunosup-
Medicine).
antibodies regarding their effect on immune cells.
pressive or -stimulating effects on immune cells or other
Unique Feature
Conditioned Humanized / Non Humanized Mouse
Model (IZI220-01)
–
GvHD-Model in Mice (IZI220-03)
cell types can be examined.
Associated Products & Services at the Institute
–
Antigen Specic Tolerance Induction (IZI250-01)
–
Bioluminescence and Fluorescence Imaging for
Preclinical In Vivo Small Animal Studies (IZI310-01)
–
Cell Tracking (IZI310-02)
–
Cellular Function Test for Tissue-destructive Fibroblasts
(IZI530-03)
–
Cytostatic Drugs and Cell Therapeutic Drugs Screening
Assays / In Vivo Testing in Mouse Model Following
Tumor Induction (IZI360-03)
–
Monoclonal Antibodies – Generation (IZI120-01)
–
Therapeutic Mouse Model: A Human Immune System
for Testing of Active Ingredients (IZI130-02)
–
GMP Manufacturing of Monoclonal Antibodies
(IZI110-02)
Fraunhofer IZI Service Catalog | IZI220-02
FRAUNHOFER INSTITUTE FOR CELL THERAPY AND IMMUNOLOGY
GVHD-MODEL IN MICE
Prole of the Fraunhofer IZI
Immune Tolerance Group
The Fraunhofer Institute for Immunology and Cell Therapy
The goal of this group is the development of cell- and antibody-
IZI founded in April 2005 is member of the Fraunhofer
based therapeutic strategies to treat complications following
Life Sciences Alliance. Its objective being to nd solutions
hematopoietic stem cell transplantation. Novel concepts of
to specic problems at the interfaces between medicine,
immunological tolerance oriented towards immunologic and
life sciences and engineering for partners active in
therapy associated complications (e.g. GVHD) are being tested in
medicine-related industries and businesses. The Institute’s
new, in-house developed animal models.
core competencies are to be found in regenerative
medicine, or more precisely in cell-therapeutic methods of
regenerating non-functioning tissue and organs through
to the biological substitution with tissue cultivated in vitro
(tissue engineering). In order for the living organism to
accept the tissues without any difculty, it is necessary
to study cellular and immunological defense and control
mechanisms and take these into account during process
and product development. These core competencies
entail a multiplicity of tasks to be solved by new products
and processes. The Institute works especially closely with
hospital institutions, performing quality tests and clinical
studies on their behalf. Additionally it also provides
assistance in obtaining manufacturing licenses and
certications.
Fraunhofer-Institut für
Zelltherapie und Immunologie
Contact
Director
Dr. Stephan Fricke
Prof. Dr. Frank Emmrich
Immune Tolerance Group
Perlickstr. 1
Phone: +49 (0) 341 / 355 36-2205
04103 Leipzig
[email protected]
Germany
Phone:
+49 (0) 341 / 355 36-1000
Fax :
+49 (0) 341 / 355 36-9921
[email protected]
PN: IZI220-03
www.izi.fraunhofer.de
© Fraunhofer IZI, status: 04/2009
GVHD-MODEL IN MICE
Graft-versus-Host-Disease (GvHD) is still the main
Methods
Further Products & Services of this Group
hematopoietic stem cells. For treatment of GvHD the
Depending on the question the pharmaceutical candidate
–
development of new therapeutic possibilities is required.
to be tested can be applied before and after induction
Therapeutic and / or preventive effects of new candidate
of allogeneic GvHD in different doses. Clinical scores,
drugs for treatment of GvHD can be tested in vivo
peripheral blood parameters, histological / immunohisto-
through an allogeneic GvHD model. Depending on the
chemical and molecular biological methods can be used
question, allogeneic GvHD can be induced in transgeneic
to diagnose therapeutic effect. Furthermore cells can be
or wild type mice (transplantation model Balb/c o
marked in order to visualize and evaluate them by means
C57Bl/6) via transplantation of splenocyte enriched
of immunouorescence microscopy or bioluminescence
–
Antigen Specic Tolerance Induction (IZI250-01)
chyma resulting from GvHD
bone marrow cells following chemotherapy. Mice can
imaging and serologic markers (e.g. interleukins).
–
Arthritis Model in the Mouse (IZI530-01)
after transplantation. (HE
–
Assay System for Isolation of Biomarkers in
staining)
complication following allogeneic transplantation of
Left: Histological analysis of
gut after induction of wildtype
be treated before or after induction of GvHD in order to
–
Conditioned Humanized / Non Humanized Mouse
GvHD. Flattening of mucosa
Model (IZI220-01)
and (x) crypts. (HE staining
Humanized, Triple Transgenic Mouse (IZI220-02)
x 20)
Right: Histological analysis of
Associated Products & Services at the Institute
the liver of GvHD mice. Bleeding inside the liver paren-
investigate potential candidate drugs.
Arteriosclerosis / Dental Plaque (IZI510-02)
Selected Applications
–
Bioluminescence and Fluorescence Imaging for
Preclinical In Vivo Small Animal Studies (IZI310-01)
Unique Feature
The model is suitable for examination of novel candidate
–
Cartilage Destruction Model in the Mouse (IZI530-02)–
drugs regarding the therapy or prevention of GvHD.
–
Cellular Function Test for Tissue-destructive Fibroblasts
In Germany only a few centers exist, which can provide
(IZI530-03)
adequate GvHD models. The allogeneic model used in the
Fraunhofer IZI is comparably simple and cost effective as
–
Diagnosis and Therapy Model (Mouse) of Borreliosis
–
Proof of Biocompatibility and Risk Analysis (IZI130-01)
–
Therapy Model for Tissue Regeneration (Fractures)
Reference Project
there are only few special requirements to be considered
during breeding of mice. At the same time the results are
Using humanized mice a xenogeneic GvHD model was
transferable to other humanized mice and can be offered
established.
(Borrelia burgdorferi) (IZI120-08)
(IZI330-01)
as whole package.
Using humanized mice stem cell protocols were established and new stem cell sources were tested for their effect
on hematopoietic stem cell transplantations.
Fraunhofer IZI Service Catalog | IZI220-03
FRAUNHOFER INSTITUTE FOR CELL THERAPY AND IMMUNOLOGY
ANTIGEN SPECIFIC TOLERANCE
INDUCTION
Prole of the Fraunhofer IZI
Virus-Host-Interaction Group
The Fraunhofer Institute for Immunology and Cell Therapy
We are examining the intricate interactions of viruses and their
IZI founded in April 2005 is member of the Fraunhofer
host using HIV (as a model) as well as other viruses. Our main
A NEW TOOL FOR THE MODULATION OF IMMUNE RESPONSES
Life Sciences Alliance. Its objective being to nd solutions
focus is the development of new antiviral prevention and
to specic problems at the interfaces between medicine,
treatment strategies. To this end, we employ the as yet poorly
life sciences and engineering for partners active in
understood mechanisms of innate intracellular defense systems
medicine-related industries and businesses. The Institute’s
against viral intruders.
core competencies are to be found in regenerative
medicine, or more precisely in cell-therapeutic methods of
Via isolation of factors that interact with the pathogen, we identify
regenerating non-functioning tissue and organs through
new therapeutic targets. Depending on the identied factors and
to the biological substitution with tissue cultivated in vitro
their properties, we decide on the further development leading
(tissue engineering). In order for the living organism to
towards antiviral strategies and / or diagnostic tools.
accept the tissues without any difculty, it is necessary
to study cellular and immunological defense and control
Furthermore, our arsenal of specic tools and cellular modications
mechanisms and take these into account during process
is developed into the targeted modulation of immune responses.
and product development. These core competencies
entail a multiplicity of tasks to be solved by new products
In summary, we work on:
and processes. The Institute works especially closely with
–
the interaction of pathogens with their host
hospital institutions, performing quality tests and clinical
–
the modulation of the host’s immune system
studies on their behalf. Additionally it also provides
–
development of therapeutic, diagnostic, and research tools
(unique selling points)
assistance in obtaining manufacturing licenses and
certications.
–
vector development
–
offering our specic know-how, methods, and tools for service
and contract research
Fraunhofer-Institut für
Zelltherapie und Immunologie
Contact
Director
Dr. Sabine Breun
Prof. Dr. Frank Emmrich
Virus-Host-Interaction Group
Phone: +49 (0) 341 / 355 36-2506
Perlickstr. 1
[email protected]
04103 Leipzig
Dr. Jörg Baumann
Germany
Phone:
+49 (0) 341 / 355 36-1000
Virus-Host-Interaction Group
Fax :
+49 (0) 341 / 355 36-9921
Phone: +49 (0) 341 / 355 36-2505
[email protected]
PN: IZI250-01
[email protected]
www.izi.fraunhofer.de
© Fraunhofer IZI, status: 04/2009
ANTIGEN SPECIFIC TOLERANCE
INDUCTION
A NEW TOOL FOR THE MODULATION OF IMMUNE RESPONSES
Regulatory T cells (Tregs) are a subpopulation of T cells
Unique Feature
Reference Project
Further Products & Services of this Group
–
unique method for the production of antigen-specic
Preclinical studies for future in vivo applications:
–
Highly Complex cDNA Libraries (IZI250-02)
regulatory T cells (patent pending)
–
–
Screening for Compounds with Antiviral Activity
that are capable of suppressing an activation of the
immune system, and thus are a key player in tolerance
to self-antigens. Regulatory T cells keep the immune
system in balance. Activation of Tregs has been previously
–
shown, but currently available technology only allows to
activate Tregs in a non-specic way. Thus, the resulting
–
immune suppression is broad, which limits the possible
targeted preparation of the immune system for the
prevention of organ rejection after transplantation
(IZI250-03)
(also xenotransplantation)
acceptance of non-self tissue
–
acceptance of foreign tissues or cells (stem cells)
–
Cell Transduction (IZI250-05)
priming of autologous or heterologous regulatory
–
treatment of severe autoimmune diseases
–
Nanometer Pathogen-Sieb (IZI250-04)
T cells is now possible
–
treatment of life threatening allergies
Associated Products & Services at the Institute
use in therapy, as a general immune suppression often is
undesirable.
Method
–
Bioluminescence and Fluorescence Imaging for
makes it possible to induce Tregs in an antigen-specic
T cells are harvested from a blood sample, modulated and
–
GvHD-Model in Mice (IZI220-03)
way. This unique technology makes Tregs a powerful tool
activated antigen specically, followed by reinfusion.
–
Humanized, Triple Transgenic Mouse (IZI220-02)
–
Proof of Biocompatibility and Risk Analysis (IZI130-01)
Preclinical In Vivo Small Animal Studies (IZI310-01)
A new invention by Dr. Breun and Dr. Baumann now
to suppress unwanted or uncontrolled immune reactions
in a specic way. The tool is versatile; it enables the
targeted modulation of the immune response (patent
Selected Applications
pending).
–
donor-specic prevention of transplant rejection
–
antigen-specic treatment of life threatening allergies
and autoimmune diseases
–
studies of tumour specic immunity
–
tolerance induction in bone marrow transplants
Fraunhofer IZI Service Catalog | IZI250-01
FRAUNHOFER INSTITUTE FOR CELL THERAPY AND IMMUNOLOGY
HIGHLY COMPLEX cDNA LIBRARIES
Prole of the Fraunhofer IZI
Virus-Host-Interaction Group
The Fraunhofer Institute for Immunology and Cell Therapy
We are examining the intricate interactions of viruses and their
IZI founded in April 2005 is member of the Fraunhofer
host using HIV (as a model) as well as other viruses. Our main
Life Sciences Alliance. Its objective being to nd solutions
focus is the development of new antiviral prevention and
to specic problems at the interfaces between medicine,
treatment strategies. To this end, we employ the as yet poorly
life sciences and engineering for partners active in
understood mechanisms of innate intracellular defense systems
medicine-related industries and businesses. The Institute’s
against viral intruders.
core competencies are to be found in regenerative
medicine, or more precisely in cell-therapeutic methods of
Via isolation of factors that interact with the pathogen, we identify
regenerating non-functioning tissue and organs through
new therapeutic targets. Depending on the identied factors and
to the biological substitution with tissue cultivated in vitro
their properties, we decide on the further development leading
(tissue engineering). In order for the living organism to
towards antiviral strategies and / or diagnostic tools.
accept the tissues without any difculty, it is necessary
to study cellular and immunological defense and control
Furthermore, our arsenal of specic tools and cellular modications
mechanisms and take these into account during process
is developed into the targeted modulation of immune responses.
and product development. These core competencies
entail a multiplicity of tasks to be solved by new products
In summary, we work on:
and processes. The Institute works especially closely with
–
the interaction of pathogens with their host
hospital institutions, performing quality tests and clinical
–
the modulation of the host’s immune system
studies on their behalf. Additionally it also provides
–
development of therapeutic, diagnostic, and research tools
(unique selling points)
assistance in obtaining manufacturing licenses and
certications.
–
vector development
–
offering our specic know-how, methods, and tools for service
and contract research
Fraunhofer-Institut für
Zelltherapie und Immunologie
Contact
Director
Dr. Sabine Breun
Prof. Dr. Frank Emmrich
Virus-Host-Interaction Group
Phone: +49 (0) 341 / 355 36-2506
Perlickstr. 1
[email protected]
04103 Leipzig
Dr. Jörg Baumann
Germany
Phone:
+49 (0) 341 / 355 36-1000
Virus-Host-Interaction Group
Fax :
+49 (0) 341 / 355 36-9921
Phone: +49 (0) 341 / 355 36-2505
[email protected]
PN: IZI250-02
[email protected]
www.izi.fraunhofer.de
© Fraunhofer IZI, status: 04/2009
HIGHLY COMPLEX cDNA LIBRARIES
Cells, organs, and organisms are characterized by their
Method
Reference Project
Further Products & Services of this Group
collected in cDNA libraries. Through the application of
A safe, gentle and highly efcient method for extracting
Utilizing a highly complex cDNA library, the Virus-Host-
–
Antigen Specic Tolerance Induction (IZI250-01)
cDNA libraries, individual active genes can be identied in
cellular RNA is the basis for the production of highly com-
Interaction laboratory is seeking factors that are important
–
Screening for Compounds with Antiviral Activity
the cells of interest using appropriate screening methods.
plex cDNA libraries. Working with RNA requires particular
for an organism’s defense against viral pathogens (this
This enables investigations on a molecular level for the
methods and extremely careful handling by specically
project is being funded by the EU).
identication and characterization of the corresponding
trained personnel. The constructed cDNA library will be
phenotype, as well as the targeted expression or suppres-
transferred into appropriate expression vectors which can
Recently two factors have been identied which have a
sion of the respective gene. Only after a gene product can
be individually modied according to the task at hand.
strong inuence on the replication of human immuno-
be identied unequivocally, a targeted modication of
Traditional expression plasmids will be utilized as well
deciency virus (HIV). One of the factors efciently prohibits
a phenotype is feasible. cDNA libraries provide excellent
as retroviral and lentiviral vectors, in order to guarantee
the transfer of the viral genome into the nucleus. A second
–
Cell Culture Models (IZI320-01)
tools for this approach. The higher the underlying com-
stable expression of the library. Following an appropriate
factor is essential for the replication of HIV. It serves as a
–
Microarray Analysis (IZI520-06)
plexity, the more promising is the investigation.
screening method, the genes of interest will be isolated
so-called co-factor which the virus is dependent upon. If
–
Non-coding RNA Biomarkers (IZI520-01)
and identied. Screening may be performed in cell culture
such a factor is removed from the cell the virus can not
–
SNP Analysis in Human Genome (IZI320-06)
or animal models.
replicate and form progeny virus.
–
Transcriptome Analysis Using Tiling Arrays and
specic genetic expression pattern. This pattern can be
(IZI250-03)
–
Cell Transduction (IZI250-05)
–
Nanometer Pathogen-Sieb (IZI250-04)
Associated Products & Services at the Institute
Ultra-high-throughput Sequencing (IZI520-04)
Client Advantages
The mechanisms of both factors are currently being
–
high complexity
–
all steps from tissue preparation to library expression
from one hand
–
Selected Applications
potential use in a novel AIDS therapeutic strategy.
–
expression vectors can be modied according to
individual needs
investigated regarding their mode of action as well as their
isolation and identication of cellular defense
mechanisms against pathogens (see reference project)
–
isolation of growth factors or oncogenes
–
identication of cellular adhesion molecules
–
identication and isolation of genes for specic
phenotypes – in cell culture and / or animal model
Fraunhofer IZI Service Catalog | IZI250-02
FRAUNHOFER INSTITUTE FOR CELL THERAPY AND IMMUNOLOGY
SCREENING FOR COMPOUNDS
WITH ANTIVIRAL ACTIVITY
Prole of the Fraunhofer IZI
Virus-Host-Interaction Group
The Fraunhofer Institute for Immunology and Cell Therapy
We are examining the intricate interactions of viruses and their
IZI founded in April 2005 is member of the Fraunhofer
host using HIV (as a model) as well as other viruses. Our main
Life Sciences Alliance. Its objective being to nd solutions
focus is the development of new antiviral prevention and
to specic problems at the interfaces between medicine,
treatment strategies. To this end, we employ the as yet poorly
life sciences and engineering for partners active in
understood mechanisms of innate intracellular defense systems
medicine-related industries and businesses. The Institute’s
against viral intruders.
core competencies are to be found in regenerative
medicine, or more precisely in cell-therapeutic methods of
Via isolation of factors that interact with the pathogen, we identify
regenerating non-functioning tissue and organs through
new therapeutic targets. Depending on the identied factors and
to the biological substitution with tissue cultivated in vitro
their properties, we decide on the further development leading
(tissue engineering). In order for the living organism to
towards antiviral strategies and / or diagnostic tools.
accept the tissues without any difculty, it is necessary
to study cellular and immunological defense and control
Furthermore, our arsenal of specic tools and cellular modications
mechanisms and take these into account during process
is developed into the targeted modulation of immune responses.
and product development. These core competencies
entail a multiplicity of tasks to be solved by new products
In summary, we work on:
and processes. The Institute works especially closely with
–
the interaction of pathogens with their host
hospital institutions, performing quality tests and clinical
–
the modulation of the host’s immune system
studies on their behalf. Additionally it also provides
–
development of therapeutic, diagnostic, and research tools
(unique selling points)
assistance in obtaining manufacturing licenses and
certications.
–
vector development
–
offering our specic know-how, methods, and tools for service
and contract research
Fraunhofer-Institut für
Zelltherapie und Immunologie
Contact
Director
Dr. Sabine Breun
Prof. Dr. Frank Emmrich
Virus-Host-Interaction Group
Phone: +49 (0) 341 / 355 36-2506
Perlickstr. 1
[email protected]
04103 Leipzig
Dr. Jörg Baumann
Germany
Phone:
+49 (0) 341 / 355 36-1000
Virus-Host-Interaction Group
Fax :
+49 (0) 341 / 355 36-9921
Phone: +49 (0) 341 / 355 36-2505
[email protected]
PN: IZI250-03
[email protected]
www.izi.fraunhofer.de
© Fraunhofer IZI, status: 04/2009
100000
90000
internalization / fusion
80000
70000
SCREENING FOR COMPOUNDS
WITH ANTIVIRAL ACTIVITY
60000
Trim1
50000
Trim5α
40000
»uncoating«
30000
TrimCyp
20000
Vif
10000
0
RT complex
0
5
10
15
20
25
30
APOBEC
reverse
transcription
preintegration complex
Natural and synthetic molecule groups of high complexity
nuclear
transfer
provirus
PML/Ini1
Fv-1
Lv2
integration
Method
Reference Project
relevant characteristics – such as antiviral activity. To this
A specic, highly efcient in vitro test system is used to
Libraries of synthetic molecule groups are being tested for
bitor / pink: with inhibitor.
end, a highly efcient screening system is necessary.
screen single components, component groups, or entire
their antiviral properties employing retroviral vector sys-
Right: Known intracellular
libraries of natural or synthetic molecules for the presence
tems. Different screening methods are being used for this
restriction factors against
At the Fraunhofer IZI, state-of-the-art and further
of antiviral properties. The components responsible are
purpose. One project investigates the inuence of antiviral
retroviruses: Restriction factors
developed viral systems are being used to isolate factors
isolated, characterized, and tested individually or in com-
substances on early replication steps of HIV: Infection is
offer protection against ret-
that possess antiviral properties. In addition, we apply a
bination with other molecules. The main focus lies in their
being traced step by step within the cell. A second project
roviral infections by blocking
diverse range of vectors and different bioluminescence
application against multiple drug resistant virus strains.
employs a highly efcient mucosal virus transmission
the pathway of the virus inside
and uorescence detection systems.
Test systems are used under BL2 and BL3 conditions.
model. This enables the identication of substances which
the cell.
Left: Quantication of a HIV
can be utilized to nd components that possess clinically
inhibitor. Blue: without inhi-
prevent virus transmission. Prevention would be a preferred
Selected Applications
Unique Feature
choice to a therapy which is hard to conduct once the virus
has infected the organism.
–
The screenings are highly efcient. The screening systems
Existing libraries of natural or synthetic molecules
Further Products & Services of this Group
may be screened for activity against HIV and other
pathogenic viruses.
–
Antigen Specic Tolerance Induction (IZI250-01)
Based on known molecules, entire classes of modi-
–
Highly Complex cDNA Libraries (IZI250-02)
throughput. It is also possible to use a unique mucosal
cations within this molecule group, may be tested
–
Cell Transduction (IZI250-05)
transmission system.
in one go, to develop derivatives with better activity,
–
Nanometer Pathogen-Sieb (IZI250-04)
were technically modied in a way that they are superior
to the state-of-the-art systems in terms of quality and
–
stability, or bioavailability.
Associated Products & Services at the Institute
–
Defensins and Antimicrobial Peptides (IZI510-01)
–
Microarray Analysis (IZI520-06)
–
Validation and Beta-evaluation of Cell-technological
Procedures / Instruments (IZI120-05)
Fraunhofer IZI Service Catalog | IZI250-03
FRAUNHOFER INSTITUTE FOR CELL THERAPY AND IMMUNOLOGY
CELL TRANSDUCTION
VECTORS AND EXPRESSION SYSTEMS
Prole of the Fraunhofer IZI
Virus-Host-Interaction Group
The Fraunhofer Institute for Immunology and Cell Therapy
We are examining the intricate interactions of viruses and their
IZI founded in April 2005 is member of the Fraunhofer
host using HIV (as a model) as well as other viruses. Our main
Life Sciences Alliance. Its objective being to nd solutions
focus is the development of new antiviral prevention and
to specic problems at the interfaces between medicine,
treatment strategies. To this end, we employ the as yet poorly
life sciences and engineering for partners active in
understood mechanisms of innate intracellular defense systems
medicine-related industries and businesses. The Institute’s
against viral intruders.
core competencies are to be found in regenerative
medicine, or more precisely in cell-therapeutic methods of
Via isolation of factors that interact with the pathogen, we identify
regenerating non-functioning tissue and organs through
new therapeutic targets. Depending on the identied factors and
to the biological substitution with tissue cultivated in vitro
their properties, we decide on the further development leading
(tissue engineering). In order for the living organism to
towards antiviral strategies and / or diagnostic tools.
accept the tissues without any difculty, it is necessary
to study cellular and immunological defense and control
Furthermore, our arsenal of specic tools and cellular modications
mechanisms and take these into account during process
is developed into the targeted modulation of immune responses.
and product development. These core competencies
entail a multiplicity of tasks to be solved by new products
In summary, we work on:
and processes. The Institute works especially closely with
–
the interaction of pathogens with their host
hospital institutions, performing quality tests and clinical
–
the modulation of the host’s immune system
studies on their behalf. Additionally it also provides
–
development of therapeutic, diagnostic, and research tools
(unique selling points)
assistance in obtaining manufacturing licenses and
certications.
–
vector development
–
offering our specic know-how, methods, and tools for service
and contract research
Fraunhofer-Institut für
Zelltherapie und Immunologie
Contact
Director
Dr. Sabine Breun
Prof. Dr. Frank Emmrich
Virus-Host-Interaction Group
Phone: +49 (0) 341 / 355 36-2506
Perlickstr. 1
[email protected]
04103 Leipzig
Dr. Jörg Baumann
Germany
Phone:
+49 (0) 341 / 355 36-1000
Virus-Host-Interaction Group
Fax :
+49 (0) 341 / 355 36-9921
Phone: +49 (0) 341 / 355 36-2505
[email protected]
PN: IZI250-05
[email protected]
www.izi.fraunhofer.de
© Fraunhofer IZI, status: 04/2009
CELL TRANSDUCTION
VECTORS AND EXPRESSION SYSTEMS
Method
Reference Project
Further Products & Services of this Group
cells (cell lines as well as populations). Different cells react
Physical and viral systems are used for an efcient yet
Two of the transduction methods are currently being used
–
Antigen Specic Tolerance Induction (IZI250-01)
differently on existing methods of transduction. Therefore,
gentle introduction of nucleic acids into cells and tissues
for in vivo cell tracking studies in animal models. Thus, cells
–
Highly Complex cDNA Libraries (IZI250-02)
it is necessary to identify and employ the best method, as
of diverse organisms. Thus, appropriate plasmids and
are transduced with vectors, and injected into mice. Using
–
Screening for Compounds with Antiviral Activity
well as the best possible expression system for each given
vectors are chosen from among an array of existing
a bioluminescence imaging system, the cells are monitored
cell type.
systems, and modied to the customer’s needs where
non-invasively. One model studies rheumatoid arthritis,
necessary. Our in-house manufactured transfection kit
the second is used in oncologic research. Both studies
allows maximal transduction rates (up to 100 percent).
use specically developed, high efciency transduction
The efcient transduction of cell cultures and tissues is the
basis for the successful study of single gene products or
If necessary, the transfer and expression systems need
to be customized according to the respective task or cell
(IZI250-03)
–
Associated Products & Services at the Institute
and expression systems, that were developed within the
type (such as stem cells). According to the requirements,
Newly developed vector systems allow an elegant, highly
clonal or heterogenous cell populations are prepared and
efcient introduction of gene sequences in different cells
isolated. A further application is the labelling of cells –
or tissues. This may be obtained short or long-term, with
with diverse colour, uorescent, or enzymatic markers, for
and without vector integration into the cellular genome.
in vivo tracking in animal models.
framework of a new platform technology.
–
Animal Model Systems for Cardiac Ischemia –
Rat / Mouse (IZI320-07)
–
Bioluminescence and Fluorescence Imaging for
Preclinical In Vivo Small Animal Studies (IZI310-01)
–
Cell Culture Models (IZI320-01)
–
Cell Tracking (IZI310-02)
Selected Applications
–
Cellular Function Test for Tissue-destructive Fibroblasts
–
–
(IZI530-03)
Client Advantages
–
Nanometer Pathogen-Sieb (IZI250-04)
gene transfer into animal and plant cells (temporary or
tailor made expression and vector systems with an
long term gene expression, with or without integra-
array of marker genes
tion)
Conditioned Humanized / Non Humanized Mouse
Model (IZI220-01)
–
micro RNA Analysis (Expression, Localization, Targets)
(IZI520-05)
–
establishment of clonal cells or populations
–
cell labelling for in vivo tracking
–
single copy insertions on demand
–
transduction of primary, precursor and stem cells
–
Non-coding RNA Biomarkers (IZI520-01)
–
transduction efciencies of up to 100 percent
–
labelling of tumor cells for metastasis studies
–
Reprogramming of Cells – iPS (induced Pluripotent
depending on vectors and cells
Stem Cells) (IZI340-02)
Fraunhofer IZI Service Catalog | IZI250-05
FRAUNHOFER INSTITUTE FOR CELL THERAPY AND IMMUNOLOGY
BIOLUMINESCENCE AND FLUORESCENCE IMAGING FOR PRECLINICAL
IN VIVO SMALL ANIMAL STUDIES
Prole of the Fraunhofer IZI
Immunotherapy – Oncology Group
The Fraunhofer Institute for Immunology and Cell Therapy
Our aim is to develop and test new therapeutic approaches in
IZI founded in April 2005 is member of the Fraunhofer
cancer. To this end, we provide all tools necessary ranging from
Life Sciences Alliance. Its objective being to nd solutions
tissue culture, cytotoxicity assays, ow cytometry, cell sorting,
to specic problems at the interfaces between medicine,
molecular imaging (including bioluminescence imaging, uo-
life sciences and engineering for partners active in
rescence imaging, MRI and others) and various preclinical mouse
medicine-related industries and businesses. The Institute’s
models.
core competencies are to be found in regenerative
medicine, or more precisely in cell-therapeutic methods of
regenerating non-functioning tissue and organs through
to the biological substitution with tissue cultivated in vitro
(tissue engineering). In order for the living organism to
accept the tissues without any difculty, it is necessary
to study cellular and immunological defense and control
mechanisms and take these into account during process
and product development. These core competencies
entail a multiplicity of tasks to be solved by new products
and processes. The Institute works especially closely with
hospital institutions, performing quality tests and clinical
studies on their behalf. Additionally it also provides
assistance in obtaining manufacturing licenses and
certications.
Fraunhofer-Institut für
Zelltherapie und Immunologie
Contact
Director
Dr. Christoph Schimmelpfennig
Prof. Dr. Frank Emmrich
Immunotherapy – Oncology Group
Perlickstr. 1
Phone: +49 (0) 341 / 355 36-3105
04103 Leipzig
[email protected]
Germany
Phone:
+49 (0) 341 / 355 36-1000
Fax :
+49 (0) 341 / 355 36-9921
[email protected]
PN: IZI310-01
www.izi.fraunhofer.de
© Fraunhofer IZI, status: 04/2009
ventral
1000
800
BIOLUMINESCENCE AND FLUORESCENCE IMAGING FOR PRECLINICAL
IN VIVO SMALL ANIMAL STUDIES
600
400
200
dorsal
Before evaluation of new drugs in clinical trials, the
The Fraunhofer IZI offers all tools necessary for performing
safety of these drugs must be proven in preclinical
these animal studies including the Caliper / Xenogen
animal studies. This includes all testing with regard to
IVIS Spectrum Imaging system, a variety of mice strains,
pharmacokinetics, and toxicity (pharmatox, genotoxicity
and immunotoxicity).
The Fraunhofer IZI now offers bioluminescence imaging
The IVIS Spectrum system is extremely precise, cost
(BLI) for testing of immunofunctions and toxicity accord-
efcient and helps to reduce animal numbers.
Selected Applications
Injection of luc2+HT29 cells
(human colon carcinoma) in
–
BLI allows the serial investigation of a single animal over
NodScid mice. Day 0 / 4 / 12 / 18 /
including Luc- transgenic mice and a state-of-the-art
an extended period of time and represents a sensitive
26 / 32 / 39 / 46.
animal facility.
and specic guidance for histopathologic tissue
sampling
ing to the ICH, FDA, and EMEA guidelines for phase I and
II studies.
The in vivo data can be used in EMEA applications.
In analogy to these guidelines implants, surfaces and
materials also have to be investigated in in vitro and in
Methods
vivo experiments (according to the guidelines for medical
–
real time investigation of metabolic processes
(sepsis and enzyme function)
investigation of implants and biomedical products
–
imaging of treatment efciency in many applications
–
Cell Tracking (IZI310-02)
(oncology, inammation, drug metabolism and toxi-
–
Clean Room Cell Sorting (IZI310-03)
cology, neurology, metabolic disease, angiogenesis,
–
Dendritic Cells and Cytokine Induced Killer Cells
(IZI310-04)
gene expression, gene therapy, cellular adoptive,
immunotransfer, Western blot detection, 3D imaging)
products 93/42/ EEC). At the Fraunhofer IZI, these studies
Bioluminescence and uorescence imaging (BLI / FLI) is an
can be performed for implantable biomedical products
extremely powerful method for non-invasive molecular
with the focus on inammation and toxicity.
imaging of tumor size or migration of effector cells.
Associated Products & Services at the Institute
Reference Project
–
Antigen Specic Tolerance Induction (IZI250-01)
luciferase-positive tumor cells or effector cells from the
In different internal Fraunhofer projects Luziferase
–
Cell Transduction (IZI250-05)
body of the animal investigated. We are using the Caliper
transgenic animal models for the evaluation of novel cell
–
Experimental Imaging (IZI320-04)
Life Science IVIS Spectrum System. This is a high-end
therapeutic applications were established.
–
GvHD-Model in Mice (IZI220-03)
It is based on the detection of photons emitted from
Client Advantage
Further Products & Services of this Group
–
Monitoring treatment courses represents a signicant cost
BLI / FLI system allowing high sensitivity imaging including
–
Humanized, Triple Transgenic Mouse (IZI220-02)
factor and is often linked to technical difculties. In vivo
the discrimination of two different cell populations
–
Non-coding RNA Biomarkers for Oncological Diseases,
animal studies are performed using big animal groups
(spectral unmixing) and 3D imaging.
nONCOchip (IZI520-02)
that have to be sacriced at specic time points. However,
–
Proof of Biocompatibility and Risk Analysis (IZI130-01)
the follow up of an individual animal is not possible.
–
Therapy Model for Tissue Regeneration (Fractures)
(IZI330-01)
Bioluminescence imaging is a new technology allowing
the non-invasive investigation of an individual living
animal at various time points over an extended period
–
Therapeutic Mouse Model: A Human Immune System
for Testing of Active Ingredients (IZI130-02)
of time. This results in a signicant reduction of animal
numbers needed and therefore in a reduction of animal
costs.
Fraunhofer IZI Service Catalog | IZI310-01
FRAUNHOFER INSTITUTE FOR CELL THERAPY AND IMMUNOLOGY
CELL TRACKING
Prole of the Fraunhofer IZI
Immunotherapy – Oncology Group
The Fraunhofer Institute for Immunology and Cell Therapy
Our aim is to develop and test new therapeutic approaches in
IZI founded in April 2005 is member of the Fraunhofer
cancer. To this end, we provide all tools necessary ranging from
Life Sciences Alliance. Its objective being to nd solutions
tissue culture, cytotoxicity assays, ow cytometry, cell sorting,
to specic problems at the interfaces between medicine,
molecular imaging (including bioluminescence imaging, uo-
life sciences and engineering for partners active in
rescence imaging, MRI and others) and various preclinical mouse
medicine-related industries and businesses. The Institute’s
models.
core competencies are to be found in regenerative
medicine, or more precisely in cell-therapeutic methods of
regenerating non-functioning tissue and organs through
to the biological substitution with tissue cultivated in vitro
(tissue engineering). In order for the living organism to
accept the tissues without any difculty, it is necessary
to study cellular and immunological defense and control
mechanisms and take these into account during process
and product development. These core competencies
entail a multiplicity of tasks to be solved by new products
and processes. The Institute works especially closely with
hospital institutions, performing quality tests and clinical
studies on their behalf. Additionally it also provides
assistance in obtaining manufacturing licenses and
certications.
Fraunhofer-Institut für
Zelltherapie und Immunologie
Contact
Director
Dr. Christoph Schimmelpfennig
Prof. Dr. Frank Emmrich
Immunotherapy – Oncology Group
Perlickstr. 1
Phone: +49 (0) 341 / 355 36-3105
04103 Leipzig
[email protected]
Germany
Phone:
+49 (0) 341 / 355 36-1000
Fax :
+49 (0) 341 / 355 36-9921
[email protected]
PN: IZI310-02
www.izi.fraunhofer.de
© Fraunhofer IZI, status: 04/2009
2000
1500
CELL TRACKING
1000
500
Cell migration is a key aspect for the development of new
The Fraunhofer IZI offers all tools necessary for performing
drugs and the characterization of immune mechanisms
these animal studies including the Caliper / Xenogen
(e.g. oncology, adoptive cell therapy, immunology and
IVIS Spectrum Imaging system, a variety of mice strains,
haematology).
Selected Applications
Allogenic, ex vivo expanded
dendritic cells migrating to T
BLI allows the serial investigation of a single animal over
cell zones of lymphoid organs.
including Luc- transgenic mice and a state-of-the-art
an extended period of time and represents a sensitive
Day 0 / day 2 / day 7 / day 11 / day
animal facility. In addition effector cells can be transduced
and specic guidance for histopathologic tissue
17 / day 28.
The increase of immune modulating agents especially
using luciferase-containing vectors according to the needs
in the eld of transplantation medicine, results in an
of the customer. In addition, visualization of different cell
increased need to understand the migration pattern of
populations is possible.
donor and recipient cells. Also, efcient monitoring of the
kinetics and physiology of tumor metastasis is necessary
The IVIS Spectrum system is extremely precise, cost
for the development of new treatment strategies.
efcient and helps to reduce animal numbers.
Monitoring treatment courses represents a signicant cost
The in vivo data can be used in EMEA applications.
–
sampling
–
real time investigation of metabolic processes
(sepsis and enzyme function)
–
real-time investigation of tumor growth and regression
–
investigation of implants and biomedical products
in vivo imaging of treatment efciency in many
Further Products & Services of this Group
–
Bioluminescence and Fluorescence Imaging for Preclinical In Vivo Small Animal Studies (IZI310-01)
applications (oncology, inammation, drug metabolism
and toxicology, neurology, metabolic disease, angio-
–
Clean Room Cell Sorting (IZI310-03)
factor and is often linked to technical difculties. In vivo
genesis, gene expression, gene therapy, cellular adop-
–
Dendritic Cells and Cytokine Induced Killer Cells
animal studies are performed using big animal groups
tive, immunotransfer)
that have to be sacriced at specic time points. However,
(IZI310-04)
Methods
the follow up of an individual animal is not possible.
Reference Project
Associated Products & Services at the Institute
imaging of tumor size or migration of effector cells.
In different internal Fraunhofer projects Luziferase
–
Cell Transduction (IZI250-05)
It is based on the detection of photons emitted from
transgenic animal models for the evaluation of novel cell
–
Cytostatic Drugs and Cell Therapeutic Drugs Screening
of time. This results in a signicant reduction of animal
luciferase-positive tumor cells or effector cells from the
therapeutic applications were established.
numbers needed and therefore in a reduction of animal
body of the animal investigated. We are using the Caliper
costs.
Life Science IVIS Spectrum System. This is a high-end
Bioluminescence and uorescence imaging (BLI / FLI) is an
Bioluminescence imaging is a new technology allowing
extremely powerful method for non-invasive molecular
the non-invasive investigation of an individual living
animal at various time points over an extended period
Assays / In Vivo Testing in Mouse Model Following
Tumor Induction (IZI360-03)
–
GMP Manufacturing of Cell Based Medicinal Products
and Tissue Preparations (IZI110-01)
BLI / FLI system allowing high sensitivity imaging including
the discrimination of two different cell populations
–
GvHD-Model in Mice (IZI220-03)
(spectral unmixing) and 3D imaging.
–
Histology of the Mammalian Brain (IZI320-05)
–
Non-coding RNA Biomarkers (IZI520-01)
–
Ovine Large Animal Model of Stroke (IZI320-03)
–
Therapeutic Mouse Model: A Human Immune System
for Testing of Active Ingredients (IZI130-02)
Fraunhofer IZI Service Catalog | IZI310-02
FRAUNHOFER INSTITUTE FOR CELL THERAPY AND IMMUNOLOGY
CLEAN ROOM CELL SORTING
Prole of the Fraunhofer IZI
Immunotherapy – Oncology Group
The Fraunhofer Institute for Immunology and Cell Therapy
Our aim is to develop and test new therapeutic approaches in
IZI founded in April 2005 is member of the Fraunhofer
cancer. To this end, we provide all tools necessary ranging from
Life Sciences Alliance. Its objective being to nd solutions
tissue culture, cytotoxicity assays, ow cytometry, cell sorting,
to specic problems at the interfaces between medicine,
molecular imaging (including bioluminescence imaging, uo-
life sciences and engineering for partners active in
rescence imaging, MRI and others) and various preclinical mouse
medicine-related industries and businesses. The Institute’s
models.
core competencies are to be found in regenerative
medicine, or more precisely in cell-therapeutic methods of
regenerating non-functioning tissue and organs through
to the biological substitution with tissue cultivated in vitro
(tissue engineering). In order for the living organism to
accept the tissues without any difculty, it is necessary
to study cellular and immunological defense and control
mechanisms and take these into account during process
and product development. These core competencies
entail a multiplicity of tasks to be solved by new products
and processes. The Institute works especially closely with
hospital institutions, performing quality tests and clinical
studies on their behalf. Additionally it also provides
assistance in obtaining manufacturing licenses and
certications.
Fraunhofer-Institut für
Zelltherapie und Immunologie
Contact
Director
Dr. Christoph Schimmelpfennig
Prof. Dr. Frank Emmrich
Immunotherapy – Oncology Group
Perlickstr. 1
Phone: +49 (0) 341 / 355 36-3105
04103 Leipzig
[email protected]
Germany
Phone:
+49 (0) 341 / 355 36-1000
Fax :
+49 (0) 341 / 355 36-9921
[email protected]
PN: IZI310-03
www.izi.fraunhofer.de
© Fraunhofer IZI, status: 04/2009
CLEAN ROOM CELL SORTING
Client Advantage
Reference Project
Further Products & Services of this Group
ing and research of diseases.
–
modular concept of the sorter allows optimal
At the Fraunhofer IZI cell sorting is intensely used for the
–
realization of customer needs
development of cell therapeutic processes in the elds of
Cell sorting allows the purication and enrichment of a
–
optimal product protection due to location in sterile
oncology, stem cell therapy and other issues.
Cell sorting is a key technology for the development of
cell based treatment strategies and for diagnosis, monitor-
specic cell type out of a mixture of cells. Examples are
laminar air ow hood
Bioluminescence and Fluorescence Imaging for Preclinical In Vivo Small Animal Studies (IZI310-01)
–
Cell Tracking (IZI310-02)
–
Dendritic Cells and Cytokine Induced Killer Cells
(IZI310-04)
the separation of dead cells from living cells, the discrimination and elimination of apoptotic cells or the isolation
and purication of a specic cell clone.
Selected Applications
For cell sorting, the Fraunhofer IZI uses the new Beckman
sterile multiparametric high speed cell sorting
Associated Products & Services at the Institute
Coulter MoFlo II high speed cell sorter. It is equipped with
–
Cell Culture Models (IZI320-01)
three lasers and is able to detect up to 11 colors. Because
–
GMP Manufacturing of Cell Based Medicinal Products
and Tissue Preparations (IZI110-01)
of the modular structure of this sorter, the machine can
be equipped with additional lasers or lasers can easily
–
Personalized Tumor Killer-Cells (IZI360-02)
be exchanged. The sorter is located in a sterile hood,
providing optimal product and user protection.
In addition, all Miltenyi sorting devices are available (Mini-,
Midi-, CiniMax).
Fraunhofer IZI Service Catalog | IZI310-03
FRAUNHOFER INSTITUTE FOR CELL THERAPY AND IMMUNOLOGY
DENDRITIC CELLS AND CYTOKINE
INDUCED KILLER CELLS
Prole of the Fraunhofer IZI
Immunotherapy – Oncology Group
The Fraunhofer Institute for Immunology and Cell Therapy
Our aim is to develop and test new therapeutic approaches in
IZI founded in April 2005 is member of the Fraunhofer
cancer. To this end, we provide all tools necessary ranging from
Life Sciences Alliance. Its objective being to nd solutions
tissue culture, cytotoxicity assays, ow cytometry, cell sorting,
to specic problems at the interfaces between medicine,
molecular imaging (including bioluminescence imaging, uo-
life sciences and engineering for partners active in
rescence imaging, MRI and others) and various preclinical mouse
medicine-related industries and businesses. The Institute’s
models.
core competencies are to be found in regenerative
medicine, or more precisely in cell-therapeutic methods of
regenerating non-functioning tissue and organs through
to the biological substitution with tissue cultivated in vitro
(tissue engineering). In order for the living organism to
accept the tissues without any difculty, it is necessary
to study cellular and immunological defense and control
mechanisms and take these into account during process
and product development. These core competencies
entail a multiplicity of tasks to be solved by new products
and processes. The Institute works especially closely with
hospital institutions, performing quality tests and clinical
studies on their behalf. Additionally it also provides
assistance in obtaining manufacturing licenses and
certications.
Fraunhofer-Institut für
Zelltherapie und Immunologie
Contact
Director
Dr. Christoph Schimmelpfennig
Prof. Dr. Frank Emmrich
Immunotherapy – Oncology Group
Perlickstr. 1
Phone: +49 (0) 341 / 355 36-3105
04103 Leipzig
[email protected]
Germany
Phone:
+49 (0) 341 / 355 36-1000
Fax :
+49 (0) 341 / 355 36-9921
[email protected]
PN: IZI310-04
www.izi.fraunhofer.de
© Fraunhofer IZI, status: 04/2009
DENDRITIC CELLS AND CYTOKINE
INDUCED KILLER CELLS
Dendritic Cells
Selected Applications
Further Products & Services of this Group
therapeutic strategies are currently being tested in
Dendritic cells (DC) are the most important antigen-
development and production of investigational new
–
clinical studies worldwide. The Fraunhofer IZI has a lot of
presenting cells of the immune system and play a key
products for cell therapeutic applications for treatment of
experience and know-how about the regulations and
role in initiating and controlling an immune response.
malignant diseases (malignant solid tumor-like pancreatic
–
Cell Tracking (IZI310-02)
administration of cell products. Cell therapeutic products
Dendritic cells can induce either a specic immune
carcinoma, hepatocellular carcinoma, etc., hematologic
–
Clean Room Cell Sorting (IZI310-03)
for clinical studies can be generated under GMP condi-
response or can initiate tolerance against a specic
diseases)
tions at the Fraunhofer IZI.
antigen.
Treatment of malignant diseases using immune effector
cells is a very promising new eld in oncology and cell
Bioluminescence and Fluorescence Imaging for Preclinical In Vivo Small Animal Studies (IZI310-01)
Associated Products & Services at the Institute
Therefore, DC are of high interest for the development
Cytokine Induced Killer Cells
of immune cell based therapies and are currently being
–
and Tissue Preparations (IZI110-01)
tested in many clinical trials.
–
Cytokine induced killer cells (CIK) are ex vivo expanded
GMP Manufacturing of Cell Based Medicinal Products
Personalized Tumor Killer-Cells (IZI360-02)
lymphocytes that express T-cell markers and NK-cell
marker. CIK cells have a strong cytotoxicity against tumor
Unique Feature
cells in vitro and induce tumor regression in animal models. First clinical studies indicate that the administration
The Fraunhofer IZI has all tools necessary for the large-
of CIK cells in clinical studies is safe and that these cells
scale expansion of Dendritic cells and CIK cells even under
can induce clinical remissions in humans with malignant
GMP conditions. From the planning of an overall strategy
diseases.
to the application of a manufacturing authorization,
all necessary steps are coordinated by the same person
providing optimal cooperation with the customer.
Fraunhofer IZI Service Catalog | IZI310-04
FRAUNHOFER INSTITUTE FOR CELL THERAPY AND IMMUNOLOGY
CELL CULTURE MODELS
Prole of the Fraunhofer IZI
Neurorepair Group
The Fraunhofer Institute for Immunology and Cell Therapy
Our focus is on development of novel therapeutic approaches
IZI founded in April 2005 is member of the Fraunhofer
for ischemic stroke. In addition to cell culture experiments and
Life Sciences Alliance. Its objective being to nd solutions
molecular biology, specialized small and large animal models are
to specic problems at the interfaces between medicine,
used for behavioural and histological evaluation. Applied imaging
life sciences and engineering for partners active in
techniques (MRI / PET) allow in vivo monitoring of regeneration.
medicine-related industries and businesses. The Institute’s
Furthermore, we investigate principle mechanisms of cerebral
core competencies are to be found in regenerative
ischemia as well as the genetic basics of dyslexia.
medicine, or more precisely in cell-therapeutic methods of
regenerating non-functioning tissue and organs through
to the biological substitution with tissue cultivated in vitro
(tissue engineering). In order for the living organism to
accept the tissues without any difculty, it is necessary
to study cellular and immunological defense and control
mechanisms and take these into account during process
and product development. These core competencies
entail a multiplicity of tasks to be solved by new products
and processes. The Institute works especially closely with
hospital institutions, performing quality tests and clinical
studies on their behalf. Additionally it also provides
assistance in obtaining manufacturing licenses and
certications.
Fraunhofer-Institut für
Zelltherapie und Immunologie
Contact
Director
Dr. Johannes Boltze
Prof. Dr. Frank Emmrich
Neurorepair Group
Perlickstr. 1
Phone: +49 (0) 341 / 97 25-814
04103 Leipzig
[email protected]
Germany
Phone:
+49 (0) 341 / 355 36-1000
Fax :
+49 (0) 341 / 355 36-9921
[email protected]
PN: IZI320-01
www.izi.fraunhofer.de
© Fraunhofer IZI, status: 04/2009
CELL CULTURE MODELS
Investigation Methods
Reference Project
Further Products & Services of this Group
neuroprotection or neuroregeneration following ischemia.
–
caspase assays: quantication of apoptosis
A recent project evaluates the neuroprotective potential
–
They do not reect the complexity of a living organism,
–
propidium iodide staining: quantication of necrosis
of adult, stem cell containing populations from cord blood
but allow highly precise control of and inuence on
–
FACS: cell analysis
and bone marrow in relation to cell age and senescence.
–
Ovine Large Animal Model of Stroke (IZI320-03)
environmental factors and experimental design. Moreover,
–
uorescence microscopy: cell analysis and visualization
In specialized cell cultures, the hematopoietic and neuronal
–
Experimental Imaging (IZI320-04)
therapeutic mechanisms can be investigated in these sys-
–
measurement of cytokines: investigation of mediator-
differentiation potential as well as the neuroprotective
–
Histology of the Mammalian Brain (IZI320-05)
based effects
properties of cells are evaluated after oxygen and glucose
–
SNP Analysis in Human Genome (IZI320-06)
deprivation in neuronal cell and organotypic slice culture.
–
Animal Model Systems for Cardiac Ischemia –
Cell culture systems are of outstanding value for
evaluating the efcacy of cell or drug based strategies for
tems in a comparatively cost-effective manner. Cell culture
models are therefore the forefront of developing novel
therapies for ischemic stroke. In combination with small
and large animal models they also ensure continuous
improvement of such therapies. This might be important
to ensure both patient welfare as well as competitive
–
Basic mechanisms of neuroprotection following ischemia
Associated Products & Services at the Institute
investigation of drug or cell application on ischemically
–
Cell Transduction (IZI250-05)
damaged neurons
–
Clean Room Cell Sorting (IZI310-03)
detailed description of mediators (e.g. pro- / anti-
–
Highly Complex cDNA Libraries (IZI250-02)
inammation, cytokines, neuroprotection, induction of
–
GMP Manufacturing of Cell Based Medicinal Products
and Tissue Preparations (IZI110-01)
proliferation, vasogenesis)
–
cost-effective setups prior to evaluation in more complex
animal models.
evaluation of neuroprotective properties of therapeutic
approaches
–
can be investigated and veried in well controlled,
Rat / Mouse (IZI320-07)
old donors as well as cord blood samples after short and
long term cryopreservation.
–
advantages.
Unique Feature
(IZI320-02)
We investigate bone marrow specimens from young and
Selected Applications
identication and improvement of relevant therapeutic
–
Proof of Biocompatibility and Risk Analysis (IZI130-01)
mechanisms
–
Screening for Anti-aging and Regeneration Substances
–
gross time window and dose-response studies
–
early detection of limiting factors or ineffective
(IZI340-03)
–
Neural and neuronal human stem and progenitor cells
–
description of direct and indirect cellular interaction
–
comparative evaluation of different cell fractions
–
identication of and discrimination between
are differentiated into adult neuronal networks in vitro.
neuroprotective properties of (stem cell) population
Subsequently, cell cultures are subjected to oxygen
and neurogenesis in vitro
Three-dimensional Stem Cell Cultures Bone / Cartilage –
Mechanical Training (IZI330-02)
approaches
Methods
Rat Model of Focal Cerebral Ischemia (Stroke)
–
Validation and Beta-evaluation of Cell-technological
Procedures / Instruments (IZI120-05)
and glucose deprivation in specialized incubators. After
transfer to normoxic culture conditions, effects of cell or
drug application on neuronal survival can be examined.
Fraunhofer IZI Service Catalog | IZI320-01
FRAUNHOFER INSTITUTE FOR CELL THERAPY AND IMMUNOLOGY
RAT MODEL OF FOCAL CEREBRAL
ISCHEMIA (STROKE)
Prole of the Fraunhofer IZI
Neurorepair Group
The Fraunhofer Institute for Immunology and Cell Therapy
Our focus is on development of novel therapeutic approaches
IZI founded in April 2005 is member of the Fraunhofer
for ischemic stroke. In addition to cell culture experiments and
Life Sciences Alliance. Its objective being to nd solutions
molecular biology, specialized small and large animal models are
to specic problems at the interfaces between medicine,
used for behavioural and histological evaluation. Applied imaging
life sciences and engineering for partners active in
techniques (MRI / PET) allow in vivo monitoring of regeneration.
medicine-related industries and businesses. The Institute’s
Furthermore, we investigate principle mechanisms of cerebral
core competencies are to be found in regenerative
ischemia as well as the genetic basics of dyslexia.
medicine, or more precisely in cell-therapeutic methods of
regenerating non-functioning tissue and organs through
to the biological substitution with tissue cultivated in vitro
(tissue engineering). In order for the living organism to
accept the tissues without any difculty, it is necessary
to study cellular and immunological defense and control
mechanisms and take these into account during process
and product development. These core competencies
entail a multiplicity of tasks to be solved by new products
and processes. The Institute works especially closely with
hospital institutions, performing quality tests and clinical
studies on their behalf. Additionally it also provides
assistance in obtaining manufacturing licenses and
certications.
Fraunhofer-Institut für
Zelltherapie und Immunologie
Contact
Director
Dr. Johannes Boltze
Prof. Dr. Frank Emmrich
Neurorepair Group
Perlickstr. 1
Phone: +49 (0) 341 / 97 25-814
04103 Leipzig
[email protected]
Germany
Phone:
+49 (0) 341 / 355 36-1000
Fax :
+49 (0) 341 / 355 36-9921
[email protected]
PN: IZI320-02
www.izi.fraunhofer.de
© Fraunhofer IZI, status: 04/2009
RAT MODEL OF FOCAL CEREBRAL
ISCHEMIA (STROKE)
The effect of therapeutic interventions can be studied in
Investigation Methods
Reference Project
Further Products & Services of this Group
–
CT: anatomic imaging, diagnosis of tumor formation
The Neurorepair Research Group investigates the thera-
–
Cell Culture Models (IZI320-01)
detail using the rat model after transient or permanent
disruption of cerebral blood ow in the middle cerebral
and bleedings
peutic potential of regenerative cells from adult adipose
–
Ovine Large Animal Model of Stroke (IZI320-03)
–
MRI: detailed anatomic and functional imaging
tissue following ischemic stroke together with an industrial
–
Experimental Imaging (IZI320-04)
–
immunohistochemistry: detailed histological
partner from California. All transplantation studies are
–
Histology of the Mammalian Brain (IZI320-05)
investigation, optionally including the use of confocal
performed strictly in accordance to the STAIR criteria for
–
SNP Analysis in Human Genome (IZI320-06)
laser scanning or electron microscopy
quality assurance in preclinical stroke research. The study
–
Animal Model Systems for Cardiac Ischemia –
behavioral phenotyping: quantication of
involves models of transient and permanent middle cerebral
sensorimotor decits and cognitive functions
artery occlusion, dose-denition approaches, and detailed
artery.
The rat model allows easy, reliable and fast realization
of small and large scale animal studies to reveal doseresponse interactions, or to compare different routes
of administration as necessarily needed to the STAIR
–
quality assurance criteria in preclinical stroke research.
Sophisticated imaging procedures such as magnetic
histological procedures and imaging. We collaborate
resonance imaging (MRI) and methods of behavioral
phenotyping are parts of our standard therapeutic
Rat / Mouse (IZI320-07)
together with local academic partners to ensure success of
Selected Applications
Associated Products & Services at the Institute
the study. In instances of successful therapeutic evaluation,
the protocol will be subsequently tested in the large animal
–
Arthritis Model in the Mouse (IZI530-01)
complete the methodological spectrum to describe,
–
development of novel treatment strategies for stroke
stroke model, to generate convincing preclinical data as a
–
Therapeutic Mouse Model: A Human Immune System
quantify and analyze the therapeutic impact of a certain
–
evaluation of neuroprotective agents and cell
basis for clinical trial.
monitoring protocols. Detailed histological investigations
treatment.
therapies
–
–
dose-response studies, comparative evaluation of
Therapy Models (Mouse) of Chronic-inammatory
Bowel Diseases (IZI120-06)
allogenic, xenogenic and also limited autologous cell
therapy testing
Unique Feature
for Testing of Active Ingredients (IZI130-02)
–
–
Three-dimensional Stem Cell Cultures Bone / Cartilage –
Mechanical Training (IZI330-02)
administrative procedures and routes
The rat model allows cost-effective, time-saving and
–
long term investigation of safety and efcacy
detailed evaluation of numerous treatment strategies by
–
studies in old and / or premorbid subjects
numerous methods in vivo. Next to fullling the crucial
–
detailed histological characterization of therapeutic
STAIR criteria and requirements of regulatory authorities,
we can generate an optimal treatment protocol to be
success
–
dened and later tested in the translational large animal
stroke model (IZI320-03) mimicking clinical reality.
detailed sensorimotor functional evaluation and
testing
–
evaluation of novel diagnostic tools
–
investigation of innovative combined therapies
Methods
Spontaneously hypertensive rats, showing the risk prole
of many human stroke patients are subjected to transient
and permanent middle cerebral artery occlusion.
Fraunhofer IZI Service Catalog | IZI320-02
FRAUNHOFER INSTITUTE FOR CELL THERAPY AND IMMUNOLOGY
OVINE LARGE ANIMAL MODEL
OF STROKE
Prole of the Fraunhofer IZI
Ischemia Research Unit
The Fraunhofer Institute for Immunology and Cell Therapy
Our focus is on development of novel therapeutic approaches
IZI founded in April 2005 is member of the Fraunhofer
for ischemic stroke. In addition to cell culture experiments and
Life Sciences Alliance. Its objective being to nd solutions
molecular biology, specialized small and large animal models are
to specic problems at the interfaces between medicine,
used for behavioural and histological evaluation. Applied imaging
life sciences and engineering for partners active in
techniques (MRI / PET) allow in vivo monitoring of regeneration.
medicine-related industries and businesses. The Institute’s
Furthermore, we investigate principle mechanisms of cerebral
core competencies are to be found in regenerative
ischemia as well as the genetic basics of dyslexia.
medicine, or more precisely in cell-therapeutic methods of
regenerating non-functioning tissue and organs through
to the biological substitution with tissue cultivated in vitro
(tissue engineering). In order for the living organism to
accept the tissues without any difculty, it is necessary
to study cellular and immunological defense and control
mechanisms and take these into account during process
and product development. These core competencies
entail a multiplicity of tasks to be solved by new products
and processes. The Institute works especially closely with
hospital institutions, performing quality tests and clinical
studies on their behalf. Additionally it also provides
assistance in obtaining manufacturing licenses and
certications.
Fraunhofer-Institut für
Zelltherapie und Immunologie
Contact
Director
Dr. Johannes Boltze
Prof. Dr. Frank Emmrich
Department of Cell Therapy
Ischemia Research Unit
Perlickstr. 1
04103 Leipzig
Phone: +49 (0) 341 / 97 25-814
Germany
[email protected]
Phone:
+49 (0) 341 / 355 36-1000
Fax :
+49 (0) 341 / 355 36-9921
[email protected]
PN: IZI320-03
www.izi.fraunhofer.de
© Fraunhofer IZI, status: 02/2010
OVINE LARGE ANIMAL MODEL
OF STROKE
Investigation Methods
Reference Project
Further Products & Services of this Unit
all neuroprotective agents (successfully tested in rodent
In cooperation with our partners at the University of
In a recent study a neuroprotective substance is tested
–
models) have so far failed in human clinical trials. This
Leipzig, extensive state-of-the-art imaging procedures
under ambulatory clinic-like conditions. A permanent
–
is most likely due to large inter-species differences and
are used: additionally to 1.5 (Philips) or 3T (Siemens)
occlusion of the middle cerebral artery induced a focal
“up-scaling” difculties between rat and human. Thus,
MR imaging with extensive anatomical and functional
cerebral ischemia in adult animals. Together with our
–
Experimental Imaging (IZI320-04)
the experts of the international STAIR committee strongly
sequences – functional metabolic processes are visualized
partners a functional analysis of cerebral blood ow within
–
Histology of the Mammalian Brain (IZI320-05)
recommend the use of large animal models that more
using various hot-tracer in the PET. In both imaging facili-
4.5 hours after acute stroke with and without therapy was
–
SNP Analysis in Human Genome (IZI320-06)
closely relate to the situation of human stroke patients.
ties inhalative and perfusion anesthesia are established.
performed using time elapsed PET-Scan with 15O-H2O. Sub-
–
Animal Model Systems for Cardiac Ischemia –
Available primate models are not only very expensive
Behavioural phenotyping to quantify sensorimotoric
sequently magnetic resonance imaging (MRI) with routine
and ethically questionable, they mostly do not allow long
function and cognitive dysfunctions verify the clinical
sequences for stroke (t1, t2 *, T2 TSE, TOF, DWI, perfusion)
term observation for efcacy and safety. These limitations
effect of an experimental therapy. Histology and immuno-
completed the imaging procedure. Finally extensive patho-
are overcome by the unique ovine large animal model at
histology permit the verifying of therapeutic effect and
histological investigations were performed.
Fraunhofer IZI.
the hypotheses of a possible underlying mechanism by
Although rodent models are well established and reliable
tools for the development of novel therapeutic strategies,
Cell Culture Models (IZI320-01)
Rat Model of Focal Cerebral Ischemia (Stroke)
(IZI320-02)
Rat / Mouse (IZI320-07)
Associated Products & Services at the Institute
morphological and morphometrical analysis. All investiga-
–
Cartilage Destruction Model in the Mouse (IZI530-02)
tions are conducted in a blinded examination.
–
Cell Tracking (IZI310-02)
–
Diagnosis and Therapy Model (Mouse) of Borreliosis
Unique Feature
(Borrelia burgdorferi) (IZI120-08)
The ovine model is exclusively available at Fraunhofer
Selected Applications
–
–
IZI. The institute’s technical and logistical infrastructure
and extensive knowledge in the elds of model system
Preclinical evaluation of new treatment protocols under
development, monitoring, pathology and imaging
clinic-like and animal husbandry conditions can be
(together with partners) ensure a high-end methodo-
carried out within acute- and long-term studies (safety
logical portfolio from one source.
and efcacy). The model is also suitable for further study
Stem Cell Media Formulations (IZI330-03)
Therapy Model for Tissue Regeneration (Fractures)
(IZI330-01)
of innovative combination therapies, and neurological
intensive care procedures.
Methods
Due to the similar size and anatomy to human the model
Induction of cerebral ischemia is performed by a
is extremely suitable for verifying and evaluation of novel
permanent occlusion of the middle cerebral artery in adult
diagnostic imaging tools (CT / MRI / PET). Additionally to
sheep. The size of lesion and functional impact can be
extensive neuropathological investigations histologically
controlled by surgical techniques. Additionally to surgical
characterizations of the therapeutic efcacy are perform-
and microsurgical procedures also neuronavigation-
ed in explorative and quantitative manner.
assisted surgeries for specic issues (e.g. local application/
transplantation, biopsy) are performed.
Fraunhofer IZI Service Catalog | IZI320-03
FRAUNHOFER INSTITUTE FOR CELL THERAPY AND IMMUNOLOGY
EXPERIMENTAL IMAGING
Prole of the Fraunhofer IZI
Neurorepair Group
The Fraunhofer Institute for Immunology and Cell Therapy
Our focus is on development of novel therapeutic approaches
IZI founded in April 2005 is member of the Fraunhofer
for ischemic stroke. In addition to cell culture experiments and
Life Sciences Alliance. Its objective being to nd solutions
molecular biology, specialized small and large animal models are
to specic problems at the interfaces between medicine,
used for behavioural and histological evaluation. Applied imaging
life sciences and engineering for partners active in
techniques (MRI / PET) allow in vivo monitoring of regeneration.
medicine-related industries and businesses. The Institute’s
Furthermore, we investigate principle mechanisms of cerebral
core competencies are to be found in regenerative
ischemia as well as the genetic basics of dyslexia.
medicine, or more precisely in cell-therapeutic methods of
regenerating non-functioning tissue and organs through
to the biological substitution with tissue cultivated in vitro
(tissue engineering). In order for the living organism to
accept the tissues without any difculty, it is necessary
to study cellular and immunological defense and control
mechanisms and take these into account during process
and product development. These core competencies
entail a multiplicity of tasks to be solved by new products
and processes. The Institute works especially closely with
hospital institutions, performing quality tests and clinical
studies on their behalf. Additionally it also provides
assistance in obtaining manufacturing licenses and
certications.
Fraunhofer-Institut für
Zelltherapie und Immunologie
Contact
Director
Dr. Johannes Boltze
Prof. Dr. Frank Emmrich
Neurorepair Group
Perlickstr. 1
Phone: +49 (0) 341 / 97 25-814
04103 Leipzig
[email protected]
Germany
Phone:
+49 (0) 341 / 355 36-1000
Fax :
+49 (0) 341 / 355 36-9921
[email protected]
PN: IZI320-04
www.izi.fraunhofer.de
© Fraunhofer IZI, status: 04/2009
EXPERIMENTAL IMAGING
Methods
Reference Project
Further Products & Services of this Group
treatment success, but also of possible adverse events.
The impact of diagnostic and therapeutic strategies and
Modern imaging techniques performed together with
–
Cell Culture Models (IZI320-01)
MRI and PET imaging are state-of-the-art technologies for
interventions can be investigated and analyzed in small
partners from the university departments of neuroradiology
–
Rat Model of Focal Cerebral Ischemia (Stroke)
this purpose. Next to anatomical imaging of the brain,
and large animal models. Repeated insights into neuro-
and nuclear medicine are crucial tools of state-of-the-art
numerous options for functional imaging and even for
pathological processes and regeneration ensure effective
therapeutic monitoring. Moreover, challenging problems
–
Ovine Large Animal Model of Stroke (IZI320-03)
visualization of cellular and metabolic processes are
therapy monitoring.
can be solved or investigated using only imaging
–
Histology of the Mammalian Brain (IZI320-05)
possible using these modalities. In parallel, imaging
techniques. For instance, the Neurorepair Research Group
–
SNP Analysis in Human Genome (IZI320-06)
protocols relevant for stroke diagnosis and monitoring
actually investigates the anatomy of the venous drainage of
–
Animal Model Systems for Cardiac Ischemia –
The development of innovative treatment approaches
is closely linked to the continuous monitoring of the
are already in use in preclinical animal models. Moreover,
Investigation Methods
novel diagnostic tools can be developed in an efcient
manner.
(IZI320-02)
Rat / Mouse (IZI320-07)
the ovine brain. This vessel system is not yet described even
in veterinary anatomy. Moreover, migration of magnetically
–
CT: anatomic imaging, diagnosis of tumor formation
labelled cell populations can be tracked in the body non-
and bleedings
invasively.
The effective application of modern imaging modalities
–
MRI: detailed anatomic and functional imaging
requires interdisciplinary collaboration between different
–
PET: functional imaging, visualization of metabolism
scientic elds and institutions. Fraunhofer IZI therefore
–
PET / CT: parallel anatomical imaging, visualization of
collaborates with many expert imaging teams, for
Associated Products & Services at the Institute
–
Bioluminescence and Fluorescence Imaging for
Preclinical In Vivo Small Animal Studies (IZI310-01)
metabolic processes and molecular imaging
example, from the departments for diagnostic radiology
and nuclear medicine from the University of Leipzig.
Selected Applications
Unique Feature
–
development of diagnostic tools for ischemic stroke
–
early diagnosis of adverse events (tumor formation,
Combined MRI- and PET-imaging in the large animal
model.
bleedings) throughout therapy development
–
assessment of lesion size, visualization of cell
migration and brain atrophy following stroke
–
visualization of proliferation and differentiation in
the adult brain
–
identication and quantication of ber tracts
–
combined imaging for parallel anatomical and
functional imaging
–
correlation with results from behavioral phenotyping
and histology to verify therapeutic success at different
levels of regeneration
Fraunhofer IZI Service Catalog | IZI320-04
FRAUNHOFER INSTITUTE FOR CELL THERAPY AND IMMUNOLOGY
HISTOLOGY OF THE
MAMMALIAN BRAIN
Prole of the Fraunhofer IZI
Neurorepair Group
The Fraunhofer Institute for Immunology and Cell Therapy
Our focus is on development of novel therapeutic approaches
IZI founded in April 2005 is member of the Fraunhofer
for ischemic stroke. In addition to cell culture experiments and
Life Sciences Alliance. Its objective being to nd solutions
molecular biology, specialized small and large animal models are
to specic problems at the interfaces between medicine,
used for behavioural and histological evaluation. Applied imaging
life sciences and engineering for partners active in
techniques (MRI / PET) allow in vivo monitoring of regeneration.
medicine-related industries and businesses. The Institute’s
Furthermore, we investigate principle mechanisms of cerebral
core competencies are to be found in regenerative
ischemia as well as the genetic basics of dyslexia.
medicine, or more precisely in cell-therapeutic methods of
regenerating non-functioning tissue and organs through
to the biological substitution with tissue cultivated in vitro
(tissue engineering). In order for the living organism to
accept the tissues without any difculty, it is necessary
to study cellular and immunological defense and control
mechanisms and take these into account during process
and product development. These core competencies
entail a multiplicity of tasks to be solved by new products
and processes. The Institute works especially closely with
hospital institutions, performing quality tests and clinical
studies on their behalf. Additionally it also provides
assistance in obtaining manufacturing licenses and
certications.
Fraunhofer-Institut für
Zelltherapie und Immunologie
Contact
Director
Dr. Johannes Boltze
Prof. Dr. Frank Emmrich
Neurorepair Group
Perlickstr. 1
Phone: +49 (0) 341 / 97 25-814
04103 Leipzig
[email protected]
Germany
Phone:
+49 (0) 341 / 355 36-1000
Fax :
+49 (0) 341 / 355 36-9921
[email protected]
PN: IZI320-05
www.izi.fraunhofer.de
© Fraunhofer IZI, status: 04/2009
HISTOLOGY OF THE
MAMMALIAN BRAIN
Investigation Methods
Reference Project
Further Products & Services of this Group
–
overview staining: overview of infarct, tissue
If used alone, histological techniques are rarely suitable to
–
Cell Culture Models (IZI320-01)
degeneration and regenerative processes
examine spontaneous regenerative processes or experimen-
–
Rat Model of Focal Cerebral Ischemia (Stroke)
immunohistochemistry: representation of specic cell
tal regenerative processes after stroke. Nevertheless, these
patterns can enhance or inhibit regeneration. Hence,
populations and cell interactions in cell culture, rat and
tools are indispensable to study and validate regeneration
–
Ovine Large Animal Model of Stroke (IZI320-03)
apart from behavioral phenotyping and imaging tech-
sheep brain
on a cellular level or to interpret results in connection
–
Experimental Imaging (IZI320-04)
stereology: quantication of discrete cellular events
with other ndings. The Neurorepair Research Group
–
SNP Analysis in Human Genome (IZI320-06)
(e.g. density of astrocytes)
continuously researches the expansion of its histological
–
Animal Model Systems for Cardiac Ischemia –
As a highly developed organ, the mammalian brain is the
place of integration and processing of complex signals.
For this purpose a large number of different cells closely
cooperate. Almost all cell types react to ischemic stroke
with specic, acute or delayed answer patterns. Those
niques, histology is an important methodical buttress in
–
–
the examination of neuroprotective and neurorestorative
therapies. Only with these methods it is possible to regis-
–
uorescence microscopy
portfolio, including conventional and immunohistochemical
ter, quantify and evaluate processes of cellular integration,
–
confocal microscopy: representation of cellular
staining of the brain. All CNS cell populations of rat and
interactions and cellular functionality (by means of
sheep can be detected and examined for interactions.
surface molecules)
Overview pathology due to ischemic stroke is also part of
staining techniques: representation of cell homing and
this examination spectrum.
differentiation, and therapeutic modulation.
–
Unique Feature
integration
(IZI320-02)
Rat / Mouse (IZI320-07)
Associated Products & Services at the Institute
–
Cell Tracking (IZI310-02)
Histological analysis enables verication of therapeutic
effects after measures of regeneration support.
Selected Applications
Furthermore, it allows us to create hypotheses on the
basic mechanisms of such effects. These hypotheses can
–
be the starting point for subsequent therapy protocol
optimization. Ideally, it is therefore possible to generate
differentiation and integration
–
not only improved therapy protocols, but also knowledge
for trade mark rights.
description of processes of cellular migration,
description of processes of degeneration and
regeneration after stroke
–
description of therapeutic inuence on nerve cells
and glia
–
Methods
safety and quality control: screening for tumor growth
after cell therapy or local inammation reactions after
application of allogenic and xenogenic material
Conventional staining techniques and immunohisto-
–
representation of neuro-, vaso- and glia genesis
chemical procedures are used. Histological methodology
–
representation of cellular processes as a correlate of
is very complex and is directed towards the particular
regeneration
case.
Fraunhofer IZI Service Catalog | IZI320-05
FRAUNHOFER INSTITUTE FOR CELL THERAPY AND IMMUNOLOGY
SNP ANALYSIS IN HUMAN GENOME
Prole of the Fraunhofer IZI
Neurorepair Group
The Fraunhofer Institute for Immunology and Cell Therapy
Our focus is on development of novel therapeutic approaches
IZI founded in April 2005 is member of the Fraunhofer
for ischemic stroke. In addition to cell culture experiments and
Life Sciences Alliance. Its objective being to nd solutions
molecular biology, specialized small and large animal models are
to specic problems at the interfaces between medicine,
used for behavioural and histological evaluation. Applied imaging
life sciences and engineering for partners active in
techniques (MRI / PET) allow in vivo monitoring of regeneration.
medicine-related industries and businesses. The Institute’s
Furthermore, we investigate principle mechanisms of cerebral
core competencies are to be found in regenerative
ischemia as well as the genetic basics of dyslexia.
medicine, or more precisely in cell-therapeutic methods of
regenerating non-functioning tissue and organs through
to the biological substitution with tissue cultivated in vitro
(tissue engineering). In order for the living organism to
accept the tissues without any difculty, it is necessary
to study cellular and immunological defense and control
mechanisms and take these into account during process
and product development. These core competencies
entail a multiplicity of tasks to be solved by new products
and processes. The Institute works especially closely with
hospital institutions, performing quality tests and clinical
studies on their behalf. Additionally it also provides
assistance in obtaining manufacturing licenses and
certications.
Fraunhofer-Institut für
Zelltherapie und Immunologie
Contact
Director
Dr. Johannes Boltze
Prof. Dr. Frank Emmrich
Neurorepair Group
Perlickstr. 1
Phone: +49 (0) 341 / 97 25-814
04103 Leipzig
[email protected]
Germany
Phone:
+49 (0) 341 / 355 36-1000
Fax :
+49 (0) 341 / 355 36-9921
[email protected]
PN: IZI320-06
www.izi.fraunhofer.de
© Fraunhofer IZI, status: 04/2009
SNP ANALYSIS IN HUMAN GENOME
Methods
Reference Project
Further Products & Services of this Group
tant for diagnosis of diseases, compatibleness of certain
DNA is extracted from tissue, saliva or blood. In larger
Almost all diseases are a result of the combined inuences
–
Cell Culture Models (IZI320-01)
drugs, and determination of potential personal disease
studies with some hundred persons and many genetic
of external environmental factors and internal genetic fac-
–
Rat Model of Focal Cerebral Ischemia (Stroke)
risk. Furthermore, such procedures make it necessary to
markers, DNA can be aliquoted by a laboratory robot.
tors. The relation between these factor types that lead to a
examine potentially pathogenic variants in appropriate
Assay design and assay validation are performed. Geno-
disease is surprisingly static. Even for dyslexia, a reading and
–
Ovine Large Animal Model of Stroke (IZI320-03)
cohorts.
typing is done using PCR and single base extension with
writing disorder, which was tragically misinterpreted as a
–
Experimental Imaging (IZI320-04)
Genetic variations strongly inuence all sorts of diseases
and the peculiarity of certain phenotypes. This is impor-
(IZI320-02)
subsequent mass spectrometric analysis. Again, large scale
lack of intelligence, a genetic background could be found.
–
Histology of the Mammalian Brain (IZI320-05)
Most frequent variations are single base exchanges, so
studies are supported by automation. Spectre analysis and
But this background does not inuence intelligence. Due to
–
Animal Model Systems for Cardiac Ischemia –
called SNPs (single nucleotide polymorphisms). Apart
statistics are done with appropriately optimized software.
this reason specic teaching and learning techniques can
from SNPs, variations in the number of copies of certain
Rat / Mouse (IZI320-07)
help affected children, if they are diagnosed early enough.
genomic regions (CNPs, copy number polymorphisms) are
Those techniques are effective especially when they are
Associated Products & Services at the Institute
important too.
Investigation Methods
Genotyping technology GENOSNIP is surpassingly suitable
–
DNA extraction
mutations in single base pairs (SNPs) in the human genome
–
Highly Complex cDNA Libraries (IZI250-02)
to analyze almost all SNPs and most CNPs. It is based on
–
DNA aliquoting
that correlate with dyslexia. With this knowledge it would
–
GLP Studies – Differential Proteomics (Available 2009)
single base extension and MALDI-TOF. Several SNPs (up
–
assay design
be possible to estimate the individual risk very early. And
to 10) can be measured with one reaction, resulting in a
–
DNA amplication and genotyping
with early therapies in pre-school age later difculties for
–
Microarray Analysis (IZI520-06)
decreased need of sample material per analysis.
–
statistical analysis
affected children in school and work could be avoided.
–
Transcriptome Analysis Using Tiling Arrays and
applied long before the diagnostic window of current performance tests: long before school. Our aim is to identify
(IZI120-09)
Ultra-high-throughput Sequencing (IZI520-04)
Unique Feature
Selected Applications
There is an option for automated analysis in larger pro-
–
diagnosis of genetic diseases
jects. The technology is easily applicable on a wide range
–
epidemiological analysis of supposed genetic risk
of research topics where SNP- and CNP variations either
play a role or are supposed to do so.
factors
–
development of optimized therapies
(“personalized medicine”)
–
determination of genetic risk for certain diseases
Fraunhofer IZI Service Catalog | IZI320-06
FRAUNHOFER INSTITUTE FOR CELL THERAPY AND IMMUNOLOGY
ANIMAL MODEL SYSTEMS FOR
CARDIAC ISCHEMIA – RAT / MOUSE
Prole of the Fraunhofer IZI
Ischemia Research Unit
The Fraunhofer Institute for Immunology and Cell Therapy
Our focus is on development of novel therapeutic approaches
IZI founded in April 2005 is member of the Fraunhofer
for ischemic stroke. In addition to cell culture experiments and
Life Sciences Alliance. Its objective being to nd solutions
molecular biology, specialized small and large animal models are
to specic problems at the interfaces between medicine,
used for behavioural and histological evaluation. Applied imaging
life sciences and engineering for partners active in
techniques (MRI / PET) allow in vivo monitoring of regeneration.
medicine-related industries and businesses. The Institute’s
Furthermore, we investigate principle mechanisms of cerebral
core competencies are to be found in regenerative
ischemia as well as the genetic basics of dyslexia.
medicine, or more precisely in cell-therapeutic methods of
regenerating non-functioning tissue and organs through
to the biological substitution with tissue cultivated in vitro
(tissue engineering). In order for the living organism to
accept the tissues without any difculty, it is necessary
to study cellular and immunological defense and control
mechanisms and take these into account during process
and product development. These core competencies
entail a multiplicity of tasks to be solved by new products
and processes. The Institute works especially closely with
hospital institutions, performing quality tests and clinical
studies on their behalf. Additionally it also provides
assistance in obtaining manufacturing licenses and
certications.
Fraunhofer-Institut für
Zelltherapie und Immunologie
Contact
Director
Dr. Johannes Boltze
Prof. Dr. Frank Emmrich
Department of Cell Therapy
Ischemia Research Unit
Perlickstr. 1
04103 Leipzig
Phone: +49 (0) 341 / 97 25-814
Germany
[email protected]
Phone:
+49 (0) 341 / 355 36-1000
Fax :
+49 (0) 341 / 355 36-9921
[email protected]
PN: IZI320-07
www.izi.fraunhofer.de
© Fraunhofer IZI, status: 02/2010
ANIMAL MODEL SYSTEMS FOR
CARDIAC ISCHEMIA – RAT / MOUSE
Background
The small animal systems facilitate quick and straight-
–
forward studies to verify the effectiveness of a therapy but
characterization and screening of stem / progenitor
Left: EImmunohistochemical
cells and isolated cardiomyocytes
analyses of rat hearts (A-F) and
in vitro evaluation of active agents and culture condition
cardiac broblasts 12 weeks
(preconditioning) for further in vivo application
after myocardial infarction.
Heart disease, particularly coronary heart disease and
also detailed and extensive studies to optimize the therapy
myocardial infarction is leading cause of death worldwide.
including dose-effect relationship and various routes and
Despite a high mortality after acute coronary artery
times of application. Of primary interest is the functional
occlusion, the irreversible loss of cardiomyocytes and
characterization employing echocardiographic investiga-
the resulting process of cardiac remodeling leads to
tions over the course of time and cardiac catheterization.
progressively reduced cardiac pump function and heart
Histological and molecular biological investigations serve
failure, ultimately. The acute mortality after myocardial
to objectify success of therapy on cellular and molecular
infarction decreased in the past years due to improved
level as well as to comprehend parakrine mechanisms
early recognition and timely start of therapy. However,
and to identify new therapeutic targets. These studies are
–
evaluation of cardioprotective agents and cell therapies
there are only limited therapies available to effectively
established in small laboratory animals (rats, and also mice
–
allogenic and xenogenic cell therapy
treat impaired heart function and developing heart failure.
in order to investigate genetically modied organisms).
–
dose-effect studies and evaluation of application-
–
Right: Overview of rat (A and
B, Masson Trichrome) and
Selected Applications
weeks after sham operation
–
Studies in large animals (sheep / pig) are in preparation.
Aims
development of novel therapeutic strategies to treat
(A) myocardial infarction (B
myocardial infarction
and C).
–
long term studies of safety and efcacy
–
–
functional and histological characterization of success
–
–
Ovine Large Animal Model of Stroke (IZI320-03)
new therapeutic targets
–
Experimental Imaging (IZI320-04)
analysis of novel drug delivery technologies evaluation
–
Histology of the Mammalian Brain (IZI320-05)
of diagnostic-therapeutic markers.
–
SNP-Analysis in Human Genome (IZI320-06)
of myocardial infarction and ischemia / reperfusion injury.
coronary artery. The ligature can be removed to establish
Furthermore, the underlying mechanisms are studied in
reperfusion after various periods of time as needed.
order to enhance and optimize the treating process as to
Therapeutics (cells or agents) can be applied p.o., s.c., i.v.,
improve cardiac pump function.
or by direct intramyocardial injections. Also pretreatment
The applied in vivo models of ischemic heart disease build
to induce pathophysiologically relevant conditions (age,
the basis for further investigations of mechanisms and
diabetes, ischemic or hypoxic preconditioning) is possible.
effectiveness of a variety of cell-based and cardioprotective
ischemic preconditioning are investigated as well as
therapeutic strategies. Moreover, they can be utilized to
strategies for an effective application of cardioprotective
analyze new drug delivery technologies and to test different
agents tested. These studies aspire to provide protection
Investigation methods
diagnostic and therapeutic markers.
to the cardiomyocytes from ischemic or stress-induced
injury.
–
–
–
The effectiveness of therapeutic strategies to treat myocardial infarction is investigated in animal model systems
of cardiac ischemia. Additionally, methods to protect
cardiomyocytes against ischemic injury can be developed
–
Associated Products & Services at the Institute
–
Assay System for Isolation of Biomarkers in
Arteriosclerosis / Dental Plaque (IZI510-02)
–
Cell Transduction (IZI250-05)
–
Developmental Toxicity of Additives, Compounds,
Supplements and Biomaterials (IZI330-04)
echocardiography: investigations over the course of
Summary
–
heart function
The group aims to develop cardioprotective and therapeutic
–
histology und Immunohistochemistry: measurements
strategies for ischemic heart disease. The effectiveness
of infarct size and detailed histological investigation
regarding relevant functional parameters and the
–
Stem Cell Media Formulations (IZI330-03)
including labeled cells
underlying mechanisms are studied in in vivo models of
–
Therapy Models (Mouse) of Chronic-inammatory
molecular biology: analysis of gene / protein expression
myocardial infarction, ischemia/reperfusion and ischemic
proles and signal transduction cascades
preconditioning.
time for morphological and functional characterization
Animal model systems for cardiac ischemia
Rat Model of Focal Cerebral Ischemia (Stroke)
characterization of mechanisms and identication of
Myocardial ischemia is induced by ligation of the left
–
Cell Culture Models (IZI320-01)
(IZI320-02)
of a therapy
–
tegies for ischemic heart disease in small animal models
In further studies, cardioprotective mechanisms and
Further Products & Services of this Unit
specic procedures (times and routes)
Methods
The group aims to develop cell-based therapeutic stra-
mouse hearts (C, native) 8
GLP Studies – Differential Proteomics (Available 2009)
(IZI120-09)
right and left heart catheterization: measurements of
Reprogramming of Cells – iPS (induced Pluripotent
Stem Cells) (IZI 340-02)
Bowel Diseases (IZI120-06)
and optimized.
Fraunhofer IZI Service Catalog | IZI320-07
FRAUNHOFER INSTITUTE FOR CELL THERAPY AND IMMUNOLOGY
THERAPY MODEL FOR TISSUE
REGENERATION (FRACTURES)
Prole of the Fraunhofer IZI
Stem Cell Technology Group
The Fraunhofer Institute for Immunology and Cell Therapy
Targeted intervention in the complex events of tissue regeneration
IZI founded in April 2005 is member of the Fraunhofer
has appeared to be technically impossible for the past decades,
Life Sciences Alliance. Its objective being to nd solutions
yet novel insights have raised hopes of directing the potential
to specic problems at the interfaces between medicine,
of pluripotent stem cells towards medical treatments and drug
life sciences and engineering for partners active in
screening. This group develops high-throughput culture methods
medicine-related industries and businesses. The Institute’s
for stem cells and optimizes the differentiation strategies of these
core competencies are to be found in regenerative
cells to develop into diverse mature cell types.
medicine, or more precisely in cell-therapeutic methods of
regenerating non-functioning tissue and organs through
to the biological substitution with tissue cultivated in vitro
(tissue engineering). In order for the living organism to
accept the tissues without any difculty, it is necessary
to study cellular and immunological defense and control
mechanisms and take these into account during process
and product development. These core competencies
entail a multiplicity of tasks to be solved by new products
and processes. The Institute works especially closely with
hospital institutions, performing quality tests and clinical
studies on their behalf. Additionally it also provides
assistance in obtaining manufacturing licenses and
certications.
Fraunhofer-Institut für
Zelltherapie und Immunologie
Contact
Director
Prof. Dr. Nicole zur Nieden
Prof. Dr. Frank Emmrich
Stem Cell Technology Group
Perlickstr. 1
Phone: +49 (0) 341 / 355 36-3305
04103 Leipzig
[email protected]
Germany
Phone:
+49 (0) 341 / 355 36-1000
Fax :
+49 (0) 341 / 355 36-9921
[email protected]
PN: IZI330-01
www.izi.fraunhofer.de
© Fraunhofer IZI, status: 04/2009
THERAPY MODEL FOR TISSUE
REGENERATION (FRACTURES)
Methods
Reference Project
Further Products & Services of this Group
bone defect is articially generated in a mouse or rat
Under anesthesia a calvarial defect of 3mm-5mm in size
Current clinical treatment of osteoporosis involves pain
–
animal model either in the calvarial bone or the femur.
will be made in non-suture-associated right parietal bone
reducing agents and anabolic bone compounds, which may
Depending on the question asked, the femur model
of a rat using a dental trephine. Alternatively, the femur
ameliorate the symptoms, but do not cure the underlying
–
Stem Cell Media Formulations (IZI330-03)
–
Developmental Toxicity of Additives, Compounds,
This model system offers the opportunity to evaluate
regeneration in mineralized bone tissue. A critical size
2
allows the examination of bone healing under stress,
head will be prepared and a 1mm size hole will be drilled.
disease. Stem cells however, may turn out to be the only
whereas the calvarial model is not load-bearing.
Both defects are so-called critical size defects as they are
real treatment for osteoporosis as they can replace the
unable to spontaneously heal by themselves. Stem cell
malfunctioning bone cells.
–
calvarial defect model
–
burr hole model
Three-dimensional Stem Cell Cultures Bone / Cartilage –
Mechanical Training (IZI330-02)
Supplements and Biomaterials (IZI330-04)
–
preparations or drugs / carrier material are applied locally.
(Stem Cell) Cytotoxicity of Additives, Compounds,
Supplements and Biomaterials (IZI330-05)
Using the described method, Fraunhofer IZI is currently testing innovative biomaterials, which are thought to support
Selected Applications
the secretion of novel bone matrix. Mesenchymal stem cells
Associated Products & Services at the Institute
are harvested and expanded in culture. Prior to transplanta–
development of various therapies for the treatment of
tion, cells are combined with the carrier biomaterials and
–
Arthritis Model in the Mouse (IZI530-01)
osteodegenerative diseases
differentiated in vitro. Then, the biomaterial-cell-composite
–
Bioluminescence and Fluorescence Imaging for
–
testing of carrier material, scaffolds, biomaterials
is introduced into the defect. Alternatively, the group aims
–
screening of anabolic / catabolic bone compounds
at evaluating embryonic stem cells (model system mouse
Preclinical In Vivo Small Animal Studies (IZI310-01)
–
(Salmonella enterica) (IZI120-07)
and primate) for their use in bone regeneration and is
mostly using the femur model for that purpose.
Diagnosis and Therapy Model (Mouse) of Salmonellosis
–
GMP Manufacturing of Cell Based Medicinal Products
and Tissue Preparations (IZI110-01)
–
GvHD-Model in Mice (IZI220-03)
–
Ovine Large Animal Model of Stroke (IZI320-03)
–
Proof of Biocompatibility and Risk Analysis (IZI130-01)
–
Reprogramming of Cells – iPS (induced Pluripotent
Stem Cells) (IZI340-02)
Fraunhofer IZI Service Catalog | IZI330-01
FRAUNHOFER INSTITUTE FOR CELL THERAPY AND IMMUNOLOGY
THREE-DIMENSIONAL STEM
CELL CULTURES BONE / CARTILAGE –
MECHANICAL TRAINING
Prole of the Fraunhofer IZI
Stem Cell Technology Group
The Fraunhofer Institute for Immunology and Cell Therapy
Targeted intervention in the complex events of tissue regeneration
IZI founded in April 2005 is member of the Fraunhofer
has appeared to be technically impossible for the past decades,
Life Sciences Alliance. Its objective being to nd solutions
yet novel insights have raised hopes of directing the potential
to specic problems at the interfaces between medicine,
of pluripotent stem cells towards medical treatments and drug
life sciences and engineering for partners active in
screening. This group develops high-throughput culture methods
medicine-related industries and businesses. The Institute’s
for stem cells and optimizes the differentiation strategies of these
core competencies are to be found in regenerative
cells to develop into diverse mature cell types.
medicine, or more precisely in cell-therapeutic methods of
regenerating non-functioning tissue and organs through
to the biological substitution with tissue cultivated in vitro
(tissue engineering). In order for the living organism to
accept the tissues without any difculty, it is necessary
to study cellular and immunological defense and control
mechanisms and take these into account during process
and product development. These core competencies
entail a multiplicity of tasks to be solved by new products
and processes. The Institute works especially closely with
hospital institutions, performing quality tests and clinical
studies on their behalf. Additionally it also provides
assistance in obtaining manufacturing licenses and
certications.
Fraunhofer-Institut für
Zelltherapie und Immunologie
Contact
Director
Prof. Dr. Nicole zur Nieden
Prof. Dr. Frank Emmrich
Stem Cell Technology Group
Perlickstr. 1
Phone: +49 (0) 341 / 355 36-3305
04103 Leipzig
[email protected]
Germany
Phone:
+49 (0) 341 / 355 36-1000
Fax :
+49 (0) 341 / 355 36-9921
[email protected]
PN: IZI330-02
www.izi.fraunhofer.de
© Fraunhofer IZI, status: 04/2009
THREE-DIMENSIONAL STEM
CELL CULTURES BONE / CARTILAGE –
MECHANICAL TRAINING
Methods
Reference Project
Further Products & Services of this Group
duces great variability between the cultures and makes
Stem cells are inoculated into the vessels and cultivated in
Until recently, all efforts to cultivate embryonic stem cells in
–
the propagation of cells very labor intensive. For the clini-
suspension with constant stirring of the medium. Samples
suspension while maintaining their pluripotent state have
cal implementation of stem cell technology it is of utmost
can be taken at specied times and testing of microcarrier
been accompanied by excessive agglomeration of the cells
–
Stem Cell Media Formulations (IZI330-03)
importance that stem cells undergo production processes
material is possible. The usage of various bioreactor mod-
and therefore seemed unsuccessful. Moreover, only a few
–
Developmental Toxicity of Additives, Compounds,
devoid of human handling without loosing their stem cell
els allows for testing the optional automation. Oxygen
groups have succeeded to expand other stem cells in sus-
characteristics. Bioreactors are suitable for manufacturing
and temperature can be varied.
pension (i.e. mesenchymal stem cells). The 3D-cultivation
Current methods for the cultivation of stem cells involve
their expansion in static culture asks. This method intro-
Selected Applications
–
the microenvironment and shear conditions in the
bioreactors seem to positively inuence stem cell charac-
–
–
teristics.
–
Supplements and Biomaterials (IZI330-05)
Associated Products & Services at the Institute
development of various therapies for the treatment of
cells in 3D is also possible. Here, protocols for steering stem
osteodegenerative diseases
cells into osteoblasts, chondrocytes and cardiomyocytes
–
Arthritis Model in the Mouse (IZI530-01)
characterization of suspension media and media
have been established.
–
Cartilage Destruction Model in the Mouse (IZI530-02)
additives (growth factors, small molecules)
–
Cell Culture Models (IZI320-01)
identication of signal transduction cascades involved
–
GMP Manufacturing of Cell Based Medicinal Products
and Tissue Preparations (IZI110-01)
in suspension culture
Unique Feature
Fraunhofer IZI uses a unique set of bioreactors; among
them a computer controlled one, in which the parallel
–
cell therapy
–
toxicity screening
–
biomechanical training of cells prior to transplantation
–
Proof of Biocompatibility and Risk Analysis (IZI130-01)
in mechanically active tissue (i.e. heart, bone)
–
Rat Model of Focal Cerebral Ischemia (Stroke)
–
simulation is possible, culture parameters (pH, pO2) are
Optimierung der Kryokonservierung von Zellen und
Geweben (IZI340-1)
(IZI320-02)
cultivation of 8 vessels is achievable. Shear stress
regulated online. Cultivation under GLP is possible.
(Stem Cell) Cytotoxicity of Additives, Compounds,
and differentiation capacity of the cells is not lost even after
long-term culture in suspension. Differentiation of stem
as pH, temperature and oxygen tension. Furthermore,
they allow controlling these parameters online. Moreover,
Supplements and Biomaterials (IZI330-04)
expansion over conventional static culture. The potency
Such bioreactor systems are advantageous in terms of
monitoring cellular microenvironmental conditions, such
(IZI330-01)
method of Fraunhofer IZI however, allows for a 31-fold
large numbers of cells at reproducible lot-to-lot quality.
Therapy Model for Tissue Regeneration (Fractures)
–
Reprogramming of Cells – iPS (induced Pluripotent
Stem Cells) (IZI340-2)
Fraunhofer IZI Service Catalog | IZI330-02
FRAUNHOFER INSTITUTE FOR CELL THERAPY AND IMMUNOLOGY
STEM CELL MEDIA FORMULATIONS
Prole of the Fraunhofer IZI
Stem Cell Technology Group
The Fraunhofer Institute for Immunology and Cell Therapy
Targeted intervention in the complex events of tissue regeneration
IZI founded in April 2005 is member of the Fraunhofer
has appeared to be technically impossible for the past decades,
Life Sciences Alliance. Its objective being to nd solutions
yet novel insights have raised hopes of directing the potential
to specic problems at the interfaces between medicine,
of pluripotent stem cells towards medical treatments and drug
life sciences and engineering for partners active in
screening. This group develops high-throughput culture methods
medicine-related industries and businesses. The Institute’s
for stem cells and optimizes the differentiation strategies of these
core competencies are to be found in regenerative
cells to develop into diverse mature cell types.
medicine, or more precisely in cell-therapeutic methods of
regenerating non-functioning tissue and organs through
to the biological substitution with tissue cultivated in vitro
(tissue engineering). In order for the living organism to
accept the tissues without any difculty, it is necessary
to study cellular and immunological defense and control
mechanisms and take these into account during process
and product development. These core competencies
entail a multiplicity of tasks to be solved by new products
and processes. The Institute works especially closely with
hospital institutions, performing quality tests and clinical
studies on their behalf. Additionally it also provides
assistance in obtaining manufacturing licenses and
certications.
Fraunhofer-Institut für
Zelltherapie und Immunologie
Contact
Director
Prof. Dr. Nicole zur Nieden
Prof. Dr. Frank Emmrich
Stem Cell Technology Group
Perlickstr. 1
Phone: +49 (0) 341 / 355 36-3305
04103 Leipzig
[email protected]
Germany
Phone:
+49 (0) 341 / 355 36-1000
Fax :
+49 (0) 341 / 355 36-9921
[email protected]
PN: IZI330-03
www.izi.fraunhofer.de
© Fraunhofer IZI, status: 04/2009
STEM CELL MEDIA FORMULATIONS
Methods
Reference Project
Further Products & Services of this Group
culture conditions may affect the number of possible
The features of the stem cells will be characterized and
Fraunhofer IZI has used the embryonic stem cell model,
–
population doublings in vitro. Furthermore, stem cells
adequate in vitro culture methods dened. The most
which based on the pluripotency of this type of stem cell
must be optimally differentiated into a cell type of
efcient means to generate cardiomyocytes, nerve cells,
is the most difcult to steer. In the past, Fraunhofer IZI has
interest. Fraunhofer IZI therefore offers customer oriented
osteoblasts, chondrocytes, adipocytes or hepatocytes will
primarily worked on the optimization of the osteogenic
solutions for the denition and optimization of stem cell
be identied.
differentiation program of these cells. Overall, a differen-
When novel stem cells are isolated from tissues, they need
to be adequately expanded in culture. Most importantly,
expansion and differentiation media.
(IZI330-01)
–
(Stem Cell) Cytotoxicity of Additives, Compounds,
Supplements and Biomaterials (IZI330-05)
In order to guarantee a consistent quality of stem cell
–
Fraunhofer IZI can base the optimization and development
of stem cell culture media on a comprehensive under-
Developmental Toxicity of Additives, Compounds,
Supplements and Biomaterials (IZI330-04)
–
Selected Applications
Client Advantage
Three-dimensional Stem Cell Cultures Bone / Cartilage –
Mechanical Training (IZI330-02)
–
tiation outcome of over 90 percent osteoblasts using the
appropriate serum can be achieved.
Therapy Model for Tissue Regeneration (Fractures)
–
product development of serum-free media,
products, however, Fraunhofer IZI works to develop
differentiation media and propagation media
chemically dened media, which are free from serum or
development of cell therapies in preparation for GMP
serum replacer. So far, dened media compositions have
Associated Products & Services at the Institute
–
Animal Model Systems for Cardiac Ischemia –
standing of signal transduction cascades, which may
been identied, which drive the differentiation into an early
inuence the self renewal and differentiation capacity of
mesenchymal lineage. An increase in efciency in differen-
stem cells. Therefore, at Fraunhofer IZI appropriate media
tiating such a progenitor from 10 to 40 percent could be
–
Arthritis Model in the Mouse (IZI530-01)
additives can be identied for a particular stem cell type
achieved by using the appropriate media composition.
–
Cytostatic Drugs / In Vitro Testing of Tumor Stem Cells
of interest.
Currently, Fraunhofer IZI is working on optimizing the later
differentiation steps.
Rat / Mouse (IZI320-07)
for Various Solid Malignant Tumors (IZI360-01)
–
GMP Manufacturing of Cell Based Medicinal Products
and Tissue Preparations (IZI110-01)
Moreover, Fraunhofer IZI aims to dene a serum-free
–
Optimization Cell and Tissue Cryoconservation
(IZI340-01)
media for expanding cultures of these stem cells, which
abdicates LIF. This dened media will reduce the cultivation
–
Ovine Large Animal Model of Stroke (IZI320-03)
of embryonic stem cells by a third of the current costs.
–
Reprogramming of Cells – iPS (induced Pluripotent
Stem Cells) (IZI340-02)
–
Screening for Anti-aging and Regeneration Substances
(IZI340-03)
Fraunhofer IZI Service Catalog | IZI330-03
FRAUNHOFER INSTITUTE FOR CELL THERAPY AND IMMUNOLOGY
DEVELOPMENTAL TOXICITY OF
ADDITIVES, COMPOUNDS, SUPPLEMENTS AND BIOMATERIALS
Prole of the Fraunhofer IZI
Stem Cell Technology Group
The Fraunhofer Institute for Immunology and Cell Therapy
Targeted intervention in the complex events of tissue regeneration
IZI founded in April 2005 is member of the Fraunhofer
has appeared to be technically impossible for the past decades,
Life Sciences Alliance. Its objective being to nd solutions
yet novel insights have raised hopes of directing the potential
to specic problems at the interfaces between medicine,
of pluripotent stem cells towards medical treatments and drug
life sciences and engineering for partners active in
screening. This group develops high-throughput culture methods
medicine-related industries and businesses. The Institute’s
for stem cells and optimizes the differentiation strategies of these
core competencies are to be found in regenerative
cells to develop into diverse mature cell types.
medicine, or more precisely in cell-therapeutic methods of
regenerating non-functioning tissue and organs through
to the biological substitution with tissue cultivated in vitro
(tissue engineering). In order for the living organism to
accept the tissues without any difculty, it is necessary
to study cellular and immunological defense and control
mechanisms and take these into account during process
and product development. These core competencies
entail a multiplicity of tasks to be solved by new products
and processes. The Institute works especially closely with
hospital institutions, performing quality tests and clinical
studies on their behalf. Additionally it also provides
assistance in obtaining manufacturing licenses and
certications.
Fraunhofer-Institut für
Zelltherapie und Immunologie
Contact
Director
Prof. Dr. Nicole zur Nieden
Prof. Dr. Frank Emmrich
Stem Cell Technology Group
Perlickstr. 1
Phone: +49 (0) 341 / 355 36-3305
04103 Leipzig
[email protected]
Germany
Phone:
+49 (0) 341 / 355 36-1000
Fax :
+49 (0) 341 / 355 36-9921
[email protected]
PN: IZI330-04
www.izi.fraunhofer.de
© Fraunhofer IZI, status: 04/2009
DEVELOPMENTAL TOXICITY OF
ADDITIVES, COMPOUNDS, SUPPLEMENTS AND BIOMATERIALS
Methods
Reference Project
Further Products & Services of this Group
tional new drug application. However, other substances,
The classic embryonic stem cell test evaluates the
Fraunhofer IZI has successfully substituted the semi-
–
such as chemicals and paints now also have to undergo
embryotoxic potential of substances by comparing their
quantitative counting of contracting cardiomyocyte clusters,
such testing as mandatory through the REACH directive.
cytotoxicity (as measured per MTT assay) to the inhibition
which is utilized as an endpoint in the classic EST, with
Whereas animal testing has been widely used in the
of differentiation (stem cell assay) in the endpoint heart
molecular tissue-specic endpoints. The improved EST now
past to evaluate such side effects, innovative in vitro
development. Mouse embryonic stem cells will be
additionally comprises the differentiation of the stem cells
–
Stem Cell Media Formulations (IZI330-03)
assays now offer the added advantage of being more
differentiated under the inuence of test compound (also:
into other tissue endpoints, such as neuronal cells, bone
–
(Stem Cell) Cytotoxicity of Additives, Compounds,
cost effective. The embryonic stem cell test (EST) is the
chemicals, biomaterials, nanomaterials). The inuence on
and cartilage. These new endpoints are especially important
currently most promising in vitro developmental toxicity
the differentiation capacity of the stem cells will be evalu-
since the heart is not the only organ susceptible to embryo-
test and comprises the target organs heart, nerves, bone
ated through measuring the expression of tissue specic
toxic effects. Often, skeletal malformations can be found in
and cartilage.
genes and concentration curves will be generated.
newborns, which have been caused by compound contact
The evaluation of potentially harmful side effects of
pharmaceutical compounds is required for an investiga-
Therapy Model for Tissue Regeneration (Fractures)
(IZI330-01)
–
Three-dimensional Stem Cell Cultures Bone / Cartilage –
Mechanical Training (IZI330-02)
Supplements and Biomaterials (IZI330-05)
Associated Products & Services at the Institute
during pregnancy. The usage of such new molecular
markers already allowed for the correct classication of the
Client Advantage
Selected Applications
The EST has been validated in a European wide study and
–
comparison to their in vivo embryotoxicity and is currently
product development pharma, food, cosmetics,
enhanced to function in an automated manner. In order to
nanomaterials
make these innovative changes to the assay, Fraunhofer IZI
testing of compound teratogenicity (i.e. pharma-
is partnering with the German Ministry for Risk Assessment
This test allows for a relatively inexpensive prescreening of
ceuticals, cosmetics, household chemicals, agro-
and DASGIP AG.
substances in an adequate time frame of eight days per
chemicals, dyes, varnish and lacquer)
can predict the developmentally harmful potential of a
given substance with a 95 percent correct predictivity.
substance.
–
–
substance evaluation according to REACH
–
Animal Model Systems for Cardiac Ischemia –
Rat / Mouse (IZI320-07)
teratogenic potential of a set of pre-validation chemicals in
–
Cellular Function Test for Tissue-destructive Fibroblasts
(IZI530-03)
–
Customized Development and Validation of Immunological In Vitro Test Systems (IZI120-04)
–
Cytostatic Drugs / In Vitro Testing of Tumor Stem Cells
for Various Solid Malignant Tumors (IZI360-01)
–
GLP Studies – Immunotoxicology (In Vitro)
(Available 2009) (IZI120-10)
–
Non-coding RNAs as Therapeutic Targets (IZI520-03)
–
Reprogramming of Cells – iPS (induced Pluripotent
Stem Cells) (IZI340-02)
–
Therapeutic Mouse Model: A Human Immune System
for Testing of Active Ingredients (IZI130-02)
Fraunhofer IZI Service Catalog | IZI330-04
FRAUNHOFER INSTITUTE FOR CELL THERAPY AND IMMUNOLOGY
(STEM CELL) CYTOTOXICITY OF
ADDITIVES, COMPOUNDS, SUPPLEMENTS AND BIOMATERIALS
Prole of the Fraunhofer IZI
Stem Cell Technology Group
The Fraunhofer Institute for Immunology and Cell Therapy
Targeted intervention in the complex events of tissue regeneration
IZI founded in April 2005 is member of the Fraunhofer
has appeared to be technically impossible for the past decades,
Life Sciences Alliance. Its objective being to nd solutions
yet novel insights have raised hopes of directing the potential
to specic problems at the interfaces between medicine,
of pluripotent stem cells towards medical treatments and drug
life sciences and engineering for partners active in
screening. This group develops high-throughput culture methods
medicine-related industries and businesses. The Institute’s
for stem cells and optimizes the differentiation strategies of these
core competencies are to be found in regenerative
cells to develop into diverse mature cell types.
medicine, or more precisely in cell-therapeutic methods of
regenerating non-functioning tissue and organs through
to the biological substitution with tissue cultivated in vitro
(tissue engineering). In order for the living organism to
accept the tissues without any difculty, it is necessary
to study cellular and immunological defense and control
mechanisms and take these into account during process
and product development. These core competencies
entail a multiplicity of tasks to be solved by new products
and processes. The Institute works especially closely with
hospital institutions, performing quality tests and clinical
studies on their behalf. Additionally it also provides
assistance in obtaining manufacturing licenses and
certications.
Fraunhofer-Institut für
Zelltherapie und Immunologie
Contact
Director
Prof. Dr. Nicole zur Nieden
Prof. Dr. Frank Emmrich
Stem Cell Technology Group
Perlickstr. 1
Phone: +49 (0) 341 / 355 36-3305
04103 Leipzig
[email protected]
Germany
Phone:
+49 (0) 341 / 355 36-1000
Fax :
+49 (0) 341 / 355 36-9921
[email protected]
PN: IZI330-05
www.izi.fraunhofer.de
© Fraunhofer IZI, status: 04/2009
(STEM CELL) CYTOTOXICITY OF
ADDITIVES, COMPOUNDS, SUPPLEMENTS AND BIOMATERIALS
Methods
Reference Project
Further Products & Services of this Group
and new materials for their potential side effects. Previous
The impairment of cellular viability by a test compounds
Fraunhofer IZI currently works together with ve European
–
assays to test for the cytotoxicity of such approval candi-
will be determined through means of classical cytotoxicity
partners on the characterization of novel biomaterials.
dates mainly used primarily isolated cells, unfortunately
assays (i.e. MTT, Live / Dead Assay, growth curves, WST).
These will be used for the development of stem cell seeded
however, their availability is often limited. In contrast
In addition, the change in tissue specic genes can be
implants and later used in humans. It is therefore critical
to primary cells, embryonic stem cells and induced
determined and concentration curves can be generated.
that these biomaterials are not negatively affecting the
–
Stem Cell Media Formulations (IZI330-03)
pluripotent stem cells represent a bottomless resource of
viability, the growth and the differentiation potential of
–
Developmental Toxicity of Additives, Compounds,
cells for such toxicity studies. Due to the differentiation
the stem cells, with which they will be combined. Further-
Investigational new drug applications and EMEA and FDA
approval require the testing of compounds, drug additives
potential of these stem cells, they can be differentiated
Applications
into any cell type of interest and more importantly to any
numbers into i.e. cardiomyocytes, nerve cells, liver cells,
(IZI330-01)
–
Three-dimensional Stem Cell Cultures Bone / Cartilage –
Mechanical Training (IZI330-02)
Supplements and Biomaterials (IZI330-04)
more, these biomaterials must not negatively inuence
endogenous stem cells as these are the cells that constantly
–
which then can be used to determine cytotoxicity.
–
product development pharma, food, cosmetics,
regenerate the body. With Fraunhofer‘s assay, the choice
nanomaterials
of materials to be used in future transplantations can be
testing of compound teratogenicity (i.e. pharma-
accelerated.
Associated Products & Services at the Institute
–
Client Advantage
chemicals, dyes, varnish and lacquer)
–
Cellular Function Test for Tissue-destructive Fibroblasts
(IZI530-03)
ceuticals, cosmetics, household chemicals, agro-
Our expertise in handling stem cells and their directed
Therapy Model for Tissue Regeneration (Fractures)
–
Conditioned Humanized / Non Humanized Mouse
Model (IZI220-01)
substance evaluation according to REACH
–
Cytostatic Drugs and Cell Therapeutic Drugs Screening
Assays / In Vivo Testing in Mouse Model Following
differentiation allows for a nearly 100 percent differentia-
Tumor Induction (IZI360-03)
tion efciency into target cells.
–
Non-coding RNAs as Therapeutic Targets (IZI520-03)
–
Therapeutic Mouse Model: A Human Immune System
for Testing of Active Ingredients (IZI130-02)
–
Validation and Beta-evaluation of Cell-technological
Procedures / Instruments (IZI120-05)
Fraunhofer IZI Service Catalog | IZI330-05
FRAUNHOFER INSTITUTE FOR CELL THERAPY AND IMMUNOLOGY
OPTIMIZATION CELL AND
TISSUE CRYOCONSERVATION
Prole of the Fraunhofer IZI
Stem Cell Biology Group
The Fraunhofer Institute for Immunology and Cell Therapy
The group combines insights from stem cell biology and bio-
IZI founded in April 2005 is member of the Fraunhofer
gerontology to develop novel strategies in regenerative medicine.
Life Sciences Alliance. Its objective being to nd solutions
We pursue a variety of innovative methods to “rejuvenate” adult
to specic problems at the interfaces between medicine,
stem cells in vitro and in vivo so that these cells can resume their
life sciences and engineering for partners active in
function as promoters of regeneration, particularly in elderly
medicine-related industries and businesses. The Institute’s
patients.
core competencies are to be found in regenerative
medicine, or more precisely in cell-therapeutic methods of
regenerating non-functioning tissue and organs through
to the biological substitution with tissue cultivated in vitro
(tissue engineering). In order for the living organism to
accept the tissues without any difculty, it is necessary
to study cellular and immunological defense and control
mechanisms and take these into account during process
and product development. These core competencies
entail a multiplicity of tasks to be solved by new products
and processes. The Institute works especially closely with
hospital institutions, performing quality tests and clinical
studies on their behalf. Additionally it also provides
assistance in obtaining manufacturing licenses and
certications.
Fraunhofer-Institut für
Zelltherapie und Immunologie
Contact
Director
Dr. Alexandra Stolzing
Prof. Dr. Frank Emmrich
Stem Cell Biology Group
Perlickstr. 1
Phone: +49 (0) 341 / 355 36-3405
04103 Leipzig
[email protected]
Germany
Phone:
+49 (0) 341 / 355 36-1000
Fax :
+49 (0) 341 / 355 36-9921
[email protected]
PN: IZI340-01
www.izi.fraunhofer.de
© Fraunhofer IZI, status: 04/2009
OPTIMIZATION CELL AND
TISSUE CRYOCONSERVATION
Ice-free cryopreservation and vitrication is established for
Client Advantage
Reference Project
and organs do not survive cryoconservation. It is not very
Few groups that work on cryopreservation evaluate
We are developing DMSO-free cryopreservation solutions
DMSO. Right: 5 percent of
well investigated if cryopreserved cells or tissue engineer-
the specic effect of temperature insults on stem cell
for stem cells together with the Serumwerke Bernburg.
DMSO.
ing products behave differently in cell therapies. What is
differentiation and biogerontology parameters. In
the long term stability of these products? Efcacy of the
collaboration with Fraunhofer experts on cell culture
cryopreservation procedure can be optimized for many
engineering, we combine insights from cell biology with
different products in regenerative medicine and might
practical product development.
some cell types, sperm and oocytes. Complex structures
blasts. Left: 10 percent of
thereby increase the in vivo potential of the products.
Further Products & Services of this Group
–
This working group is focussing on the cryopreservation
of stem cells and skin. This project is run in cooperation
Human cryoconserved bro-
Reprogramming of Cells – iPS (induced Pluripotent
Stem Cells) (IZI340-02)
Methods
–
with 3 other Fraunhofer Institutes, the IPA, IGB, and IPT.
Screening for Anti-aging and Regeneration Substances
(IZI340-03)
The IPA is developing automated cryopreservation units
–
cell cultures (stem cells, primary cells, cell lines)
that will be tested in combination with new stem cell
–
differentiation assays
cryosolutions. Our goal is to improve established protocols
–
real-time PCR
and introduce new solutions.
–
FACS analysis
–
cell sorting
Associated Products & Services at the Institute
–
GMP Manufacturing of Cell Based Medicinal Products
and Tissue Preparations (IZI110-01)
Equipment
Selected Applications
–
Stem Cell Media Formulations (IZI330-03)
–
Three-dimensional Stem Cell Cultures Bone / Cartilage –
The Fraunhofer IZI has experience with different cryopreservation strategies and systems. We use the Thermo
Mechanical Training (IZI330-02)
–
Scientic CryoMed automated cryomachine that allows
for the optimal temperature prole characterization for
optimization of chemical cryopreservation solutions
for cells and tissues
–
different cell types.
–
Validation and Beta-evaluation of Cell-technological
Procedures / Instruments (IZI120-05)
analysis of the best temperature prole for improved
cell survival
–
development of evaluation processes for improved
efciency
–
optimization of long term storage
–
development of cell banking strategies
–
optimization of short term storage for tissue and
organs (transport)
Fraunhofer IZI Service Catalog | IZI340-01
FRAUNHOFER INSTITUTE FOR CELL THERAPY AND IMMUNOLOGY
REPROGRAMMING OF CELLS – IPS
(INDUCED PLURIPOTENT STEM CELLS)
Prole of the Fraunhofer IZI
Stem Cell Biology Group
The Fraunhofer Institute for Immunology and Cell Therapy
The group combines insights from stem cell biology and bio-
IZI founded in April 2005 is member of the Fraunhofer
gerontology to develop novel strategies in regenerative medicine.
Life Sciences Alliance. Its objective being to nd solutions
We pursue a variety of innovative methods to “rejuvenate” adult
to specic problems at the interfaces between medicine,
stem cells in vitro and in vivo so that these cells can resume their
life sciences and engineering for partners active in
function as promoters of regeneration, particularly in elderly
medicine-related industries and businesses. The Institute’s
patients.
core competencies are to be found in regenerative
medicine, or more precisely in cell-therapeutic methods of
regenerating non-functioning tissue and organs through
to the biological substitution with tissue cultivated in vitro
(tissue engineering). In order for the living organism to
accept the tissues without any difculty, it is necessary
to study cellular and immunological defense and control
mechanisms and take these into account during process
and product development. These core competencies
entail a multiplicity of tasks to be solved by new products
and processes. The Institute works especially closely with
hospital institutions, performing quality tests and clinical
studies on their behalf. Additionally it also provides
assistance in obtaining manufacturing licenses and
certications.
Fraunhofer-Institut für
Zelltherapie und Immunologie
Contact
Director
Dr. Alexandra Stolzing
Prof. Dr. Frank Emmrich
Stem Cell Biology Group
Perlickstr. 1
Phone: +49 (0) 341 / 355 36-3405
04103 Leipzig
[email protected]
Germany
Phone:
+49 (0) 341 / 355 36-1000
Fax :
+49 (0) 341 / 355 36-9921
[email protected]
PN: IZI340-02
www.izi.fraunhofer.de
© Fraunhofer IZI, status: 04/2009
REPROGRAMMING OF CELLS – IPS
(INDUCED PLURIPOTENT STEM CELLS)
Adult mesenchymal stem cells were found to be aging
Equipment
Reference Project
Further Products & Services of this Group
with age. It is difcult to isolate enough adult stem cells
–
proprietary technology for non-viral iPS derivation
The company Zavita is testing nuclear transfer in mouse
–
of high quality for therapeutic applications. We therefore
–
micromanipulator for injections or nuclear transfer
oocytes. Part of this project is partial cloning, where the
and losing quality. Furthermore, cell numbers decrease
developed a process to reprogram somatic cells to
nucleus of a somatic cell is partially reprogrammed and
establish pluripotent stem cells – so-called induced pluripotent stem cells (iPS). These cells can be derived patient
Optimization Cell and Tissue Cryoconservation
(IZI340-01)
–
Screening for Anti-aging and Regeneration Substances
(IZI340-03)
then transferred back into the donor cell.
Methods
specically, are not genetically modied and increase
the chance for a smooth and fast transfer into the clinic.
–
real-time PCR
These cells have some characteristics of embryonic stem
–
methylation assay
cells, like nanog, oct4 and sox2 expression.
–
differentiation assay
Associated Products & Services at the Institute
–
Animal Model Systems for Cardiac Ischemia –
Rat / Mouse (IZI320-07)
–
pluripotency analysis
The group works on several strategies to develop iPS
–
embryoid body assay
–
Cell Transduction (IZI250-05)
cells without the use of viruses or genetic modications.
–
telomere length analysis
–
Developmental Toxicity of Additives, Compounds,
Especially formulated medium and cell-cell fusion, cell
–
telomerase activity analysis
extract reprogramming or nuclear transfer are used to
–
karyotyping
develop iPS cells.
–
comet assay
–
markers of oxidative stress & aging
Supplements and Biomaterials (IZI330-04)
–
GMP Manufacturing of Cell Based Medicinal Products
and Tissue Preparations (IZI110-01)
–
micro RNA Analysis (Expression, Localization, Targets)
(IZI520-05)
–
Stem Cell Media Formulations (IZI330-03)
Selected Applications
–
Therapy Model for Tissue Regeneration (Fractures)
–
–
Client Advantage
(IZI330-01)
The Fraunhofer IZI has expertise and experience with
the derivation of iPS cells. The extensive technical infrastructure of the institute facilitates our work.
cells can be used in research projects, but also for
therapeutic development
–
development of patient or disease specic cell lines
–
tissue engineering
–
studying signal pathways in differentiation
Three-dimensional Stem Cell Cultures Bone / Cartilage –
Mechanical Training (IZI330-02)
Fraunhofer IZI Service Catalog | IZI340-02
FRAUNHOFER INSTITUTE FOR CELL THERAPY AND IMMUNOLOGY
SCREENING FOR ANTI-AGING AND
REGENERATION SUBSTANCES
Prole of the Fraunhofer IZI
Stem Cell Biology Group
The Fraunhofer Institute for Immunology and Cell Therapy
The group combines insights from stem cell biology and bio-
IZI founded in April 2005 is member of the Fraunhofer
gerontology to develop novel strategies in regenerative medicine.
Life Sciences Alliance. Its objective being to nd solutions
We pursue a variety of innovative methods to “rejuvenate” adult
to specic problems at the interfaces between medicine,
stem cells in vitro and in vivo so that these cells can resume their
life sciences and engineering for partners active in
function as promoters of regeneration, particularly in elderly
medicine-related industries and businesses. The Institute’s
patients.
core competencies are to be found in regenerative
medicine, or more precisely in cell-therapeutic methods of
regenerating non-functioning tissue and organs through
to the biological substitution with tissue cultivated in vitro
(tissue engineering). In order for the living organism to
accept the tissues without any difculty, it is necessary
to study cellular and immunological defense and control
mechanisms and take these into account during process
and product development. These core competencies
entail a multiplicity of tasks to be solved by new products
and processes. The Institute works especially closely with
hospital institutions, performing quality tests and clinical
studies on their behalf. Additionally it also provides
assistance in obtaining manufacturing licenses and
certications.
Fraunhofer-Institut für
Zelltherapie und Immunologie
Contact
Director
Dr. Alexandra Stolzing
Prof. Dr. Frank Emmrich
Stem Cell Biology Group
Perlickstr. 1
Phone: +49 (0) 341 / 355 36-3405
04103 Leipzig
[email protected]
Germany
Phone:
+49 (0) 341 / 355 36-1000
Fax :
+49 (0) 341 / 355 36-9921
[email protected]
PN: IZI340-03
www.izi.fraunhofer.de
© Fraunhofer IZI, status: 04/2009
SCREENING FOR ANTI-AGING AND
REGENERATION SUBSTANCES
The regeneration of tissues and organs declines with
Client Advantage
Further Products & Services of this Group
levels of neurodegenerative diseases, diabetes and other
We developed different cell culture models for the analysis
–
age related diseases. The Fraunhofer IZI combines stem
of anti-aging effects of substances or pharmaceutics. An
cell technologies with knowledge from aging studies to
adult organotypic slice model was developed to analyze
develop new strategies for tissues regeneration. Different
substances or cells on brain tissues.
age. With the demographic changes, we will face higher
left 18 years / right 50 years.
–
Optimization Cell and Tissue Cryoconservation
(IZI340-1)
Middle picture: in vitro aging –
Reprogramming of Cells – iPS (induced Pluripotent
passage 5.
Stem Cells) (IZI340-2)
strategies can be studied for the in vitro and / or in vivo
Right picture: in vitro aging –
rejuvenation of stem cells, in order to improve the therapeutic effect of stem cells from old or diseased patients
Left picture: ex vivo aging –
passage 15.
Selected Applications
Associated Products & Services at the Institute
–
evaluation and manipulation of cellular aging
–
Cell Culture Models (IZI320-01)
–
reprogramming of cells
–
GLP Studies – Immunotoxicology (In Vitro)
–
analysis of substances (including, herbs, antioxidants,
and improve endogenous regeneration.
Methods
functional food) for their anti-aging effects
The Fraunhofer IZI has developed different assays for the
analysis of aging changes in cells and tissues.
(Available 2009) (IZI120-10)
–
Stem Cell Media Formulations (IZI330-03)
–
Therapeutic Mouse Model: A Human Immune System
for Testing of Active Ingredients (IZI130-02)
–
telomerase activity
–
telomere length
–
sky karyotyping
An internal project demonstrated that the aging process
–
comet assay
of mesenchymal stem cells can be slowed during
–
carbonyl-ELISA
expansion. Cells derived by this process have been proved
–
TBAR assay
effective in improving survival in a mouse bone marrow
–
mitochondrial activity
transplantation model. This knowledge will now be
–
ROS production
applied for the development of improved stem cell
–
redox potential analysis
therapies in old patients using a mouse model.
–
in vivo testing in mice
Reference Project
Fraunhofer IZI Service Catalog | IZI340-03
FRAUNHOFER INSTITUTE FOR CELL THERAPY AND IMMUNOLOGY
CYTOSTATIC DRUGS / IN VITRO TESTING OF TUMOR STEM CELLS FOR
VARIOUS SOLID MALIGNANT TUMORS
Prole of the Fraunhofer IZI
Tumor Stem Cells Group
The Fraunhofer Institute for Immunology and Cell Therapy
Our group focuses on the identication, isolation, characterization,
IZI founded in April 2005 is member of the Fraunhofer
and expansion of undifferentiated tumor stem cells from various
Life Sciences Alliance. Its objective being to nd solutions
tumor entities. One initial focus is the testing of new innovative
to specic problems at the interfaces between medicine,
cytostatic drugs as a scientic-commercial service. Our scientic
life sciences and engineering for partners active in
work centers on nding prospective specically targeted medica-
medicine-related industries and businesses. The Institute’s
tions as well as cell-based interventions aimed at various tumor
core competencies are to be found in regenerative
specic tumor stem cells.
medicine, or more precisely in cell-therapeutic methods of
regenerating non-functioning tissue and organs through
to the biological substitution with tissue cultivated in vitro
(tissue engineering). In order for the living organism to
accept the tissues without any difculty, it is necessary
to study cellular and immunological defense and control
mechanisms and take these into account during process
and product development. These core competencies
entail a multiplicity of tasks to be solved by new products
and processes. The Institute works especially closely with
hospital institutions, performing quality tests and clinical
studies on their behalf. Additionally it also provides
assistance in obtaining manufacturing licenses and
certications.
Fraunhofer-Institut für
Zelltherapie und Immunologie
Contact
Director
Dr. Peter Ruschpler
Prof. Dr. Frank Emmrich
Tumor Stem Cells Group
Perlickstr. 1
Phone: +49 (0) 341 / 355 36-2605
04103 Leipzig
[email protected]
Germany
Phone:
+49 (0) 341 / 355 36-1000
Fax :
+49 (0) 341 / 355 36-9921
[email protected]
PN: IZI360-01
www.izi.fraunhofer.de
© Fraunhofer IZI, status: 04/2009
Normalgewebe
CYTOSTATIC DRUGS / IN VITRO TESTING OF TUMOR STEM CELLS FOR
VARIOUS SOLID MALIGNANT TUMORS
Tumor stem cells (TSCs) have been found to play a signi-
Tumor
adulte Stammzellen = undiffe-
Tumorstammzellen =
renziert
tumorgen
transient amplizierte Zellen
nicht-tumorgene Tumor-
normal differenzierte Zellen
zellen
Methods
Reference Project
Left: Tumor stem cell model.
They possess the typical characteristics of stem cells,
The tumor stem cells of diverse entities are dened and
By employing breast cancer tumor stem cells, the cytostatic /
Right: Tumor stem cell culture
such as self renewal and differentiation potential. At the
characterized through immunological, ow-cytometric
cytotoxic effect of a new active agent candidate can be
of the breast carcinoma.
present time, it is assumed that this type of cell is resistant
and molecular biological analyses. Various radiation
investigated and characterized more precisely. It was shown
to various forms of therapy which leads to recidivism as
protocols can then be applied in combination with the
that the corresponding growth curve over the entire seven-
well as to metastases.
exposure of the cells as compared to IND candidates over
day kinetic course exhibited a strongly cytostatic / cytotoxic
cant role in the development of various forms of cancer.
a seven-day kinetic process. The experimental selection is
effect with an up to 40 percent reduction of the number of
At the Fraunhofer Institute for Cell Therapy and Immuno-
carried out at each kinetic time point via a 3H-thymidin
cells for a high concentration of the active agent compared
logy, a model system has been developed which enables a
proliferation assay in order to describe the vital cell
to 1 x e4 Mama_TSC each.
fast and practice-oriented investigation of multiple active
division potential after cytostatic / cytotoxic treatment.
agent candidates or investigational new drug (IND) candi-
Additionally, an analysis can be conducted regarding
ABX-CRO advanced pharmaceutical services Forschungs-
dates for intervention against tumor stem cell entities. In
the expression status of concise TSC surface antigens
gesellschaft mbH, Dresden
Assays / In Vivo Testing in Mouse Model Following
vitro sensitivity trials are conducted on specic tumor stem
(FACS), the secretion behavior with respect to TSC-specic
“Testing of the effect of the substance ACD-101 on breast
Tumor Induction (IZI360-03)
cells to test new active agent candidates. More precisely,
cytokines (EliSpot, CBA), and the expression and mutation
cancer tumor stem cells“
this means testing dose-dependent kinetics in relation to
status of specic “stem cell genes” on the mRNA and
specic radiation regimens. The testing platform primarily
DNA level (real-time PCR / DNA sequencing).
Further Products & Services of this Group
–
Personalized Tumor Killer-Cells (IZI360-02)
–
Cytostatic Drugs and Cell Therapeutic Drugs Screening
Associated Products & Services at the Institute
provides growth curves of tumor stem cells according to
–
active agent exposition, which can be supplemented by a
subsequent in vivo approach (IZI360-3) following tumor
logical In Vitro Test Systems (IZI120-04)
Selected Applications
–
genesis in a mouse model.
Customized Development and Validation of ImmunoDevelopmental Toxicity of Additives, Compounds,
Supplements and Biomaterials (IZI330-04)
New IND candidates (e.g. cytostatic drugs) can be tested
by employing characterized tumor stem cell lines of
–
Microarray Analysis (IZI520-06)
various tumor entities. The focus in this process is always
–
Monoclonal Antibodies – Generation (IZI120-01)
directed towards the selective assessment of cytotoxic
–
Non-coding RNA Biomarkers (IZI520-01)
In order to be able to utilize tumor stem cells for sub-
potential with respect to tumor stem cells. Current
–
Stem Cell Media Formulations (IZI330-03)
stance analysis, extremely highly specialized knowledge is
traditional oncological treatments remain beset by the
–
Therapeutic Mouse Model: A Human Immune System
required which allows the development of an active agent
problem of recidivism, therefore, these clinical innovations
which exclusively eliminates the tumor stem cells. Thus,
represent an advance in the eld and can be developed
the clinical goal of developing a therapy which excludes
into therapeutic strategies and eventually be used in the
non-responders or relapses is coming ever closer into the
clinic.
Unique Feature
for Testing of Active Ingredients (IZI130-02)
realm of possibility. This testing system which uses isolated and characterized tumor stem cells of various tumor
entities as a technology platform for the development of
biomedical innovations, is unique throughout Germany.
Fraunhofer IZI Service Catalog | IZI360-01
FRAUNHOFER INSTITUTE FOR CELL THERAPY AND IMMUNOLOGY
PERSONALIZED TUMOR KILLER-CELLS
Prole of the Fraunhofer IZI
Tumor Stem Cells Group
The Fraunhofer Institute for Immunology and Cell Therapy
Our group focuses on the identication, isolation, characterization,
IZI founded in April 2005 is member of the Fraunhofer
and expansion of undifferentiated tumor stem cells from various
Life Sciences Alliance. Its objective being to nd solutions
tumor entities. One initial focus is the testing of new innovative
to specic problems at the interfaces between medicine,
cytostatic drugs as a scientic-commercial service. Our scientic
life sciences and engineering for partners active in
work centers on nding prospective specically targeted medica-
medicine-related industries and businesses. The Institute’s
tions as well as cell-based interventions aimed at various tumor
core competencies are to be found in regenerative
specic tumor stem cells.
medicine, or more precisely in cell-therapeutic methods of
regenerating non-functioning tissue and organs through
to the biological substitution with tissue cultivated in vitro
(tissue engineering). In order for the living organism to
accept the tissues without any difculty, it is necessary
to study cellular and immunological defense and control
mechanisms and take these into account during process
and product development. These core competencies
entail a multiplicity of tasks to be solved by new products
and processes. The Institute works especially closely with
hospital institutions, performing quality tests and clinical
studies on their behalf. Additionally it also provides
assistance in obtaining manufacturing licenses and
certications.
Fraunhofer-Institut für
Zelltherapie und Immunologie
Contact
Director
Dr. Peter Ruschpler
Prof. Dr. Frank Emmrich
Tumor Stem Cells Group
Perlickstr. 1
Phone: +49 (0) 341 / 355 36-2605
04103 Leipzig
[email protected]
Germany
Phone:
+49 (0) 341 / 355 36-1000
Fax :
+49 (0) 341 / 355 36-9921
[email protected]
PN: IZI360-02
www.izi.fraunhofer.de
© Fraunhofer IZI, status: 04/2009
PERSONALIZED TUMOR KILLER-CELLS
Tumor stem cells (TSC) have been ascribed a signicant
Methods
role in the emergence of various forms of cancer. These
IFN-J-ELISPOT assay of a breast-
Further Products & Services of this Group
TSC-specic CD8+ cytotoxic
–
Cytostatic Drugs / In Vitro Testing of Tumor Stem Cells
cells possess typical stem cell characteristics such as self-
The tumor stem cells are co-cultured with donor lympho-
T-cell line
renewal and differentiation potential. At the present time
cytes of the corresponding HLA-class 1 compatibility in
Second bar: very severe im-
it is assumed that this type of cell is resistant to various
the allogeneic system (MLTC). Thus, there is a resulting
mune reaction of the CD8+
types of therapy and leads to recidivism as well as to
immunological “branding” of the CD8+-T-lymphocytes
cells to the breast-TSCs
Assays / In Vivo Testing in Mouse Model Following
metastases.
onto precisely this cell population to which they then
Third bar: HLA-class I restricted
Tumor Induction (IZI360-03)
for Various Solid Malignant Tumors (IZI360-01)
–
Cytostatic Drugs and Cell Therapeutic Drugs Screening
become immunoreactive (g-IFN EliSpot). The CD8+
immunoreaction of the
This product is a TSC-specic fraction of cytotoxic CD8+
population of this specication is then expanded to such
CD8+ cells to the breast-TSC
T-lymphocytes, restricted to a motif of HLA class 1,
an extent that after a “limited dilution” such an oligo-
Eighth bar: no immuno-
which exclusively recognizes and lyses the TSCs within a
clonality is produced, for which the specic monoclone
reaction of the CD8+ cells to
heterogeneous malignancy.
reaches its cytotoxic optimum and can contribute non-
healthy cells of the breast
–
Clean Room Cell Sorting (IZI310-03)
specic monoclones in addition to a GvT (graft vs. tumor)
parenchyms o thus highly
–
Dendritic Cells and Cytokine Induced Killer Cells
In addition to acquiring a testing system for new active
effect (Read out by 51Cr release assay). The challenge
specic to breast-TSC
agent candidates, we have thus gained access to a cell-
lies in the controllability of GvHD (graft vs. host disease),
based tool for intervention against TSCs as well.
which remains a simultaneous occurrence. In this context,
Associated Products & Services at the Institute
(IZI310-04)
–
Humanized, Triple Transgenic Mouse (IZI220-02)
an additional approach to an anti-CD4 treatment might
include prevention and therapy of GvHD.
Reference Project
Unique Feature
Recently, a TSC specic CD8+-CTL line of the breast cancer
Within the context of applying TSCs for the production
Selected Applications
of TSC-specic CD8+-CTL, the possibility also exists of
tumor was generated, which was able to recognize breast
TSCs, but which did not react against the cells of the
developing an innovative cell therapeutic agent, which
By producing tumor-stem-cell-specic CD8+-cytotoxic
residual tumor (depleted fraction = heterogeneous and not
eliminates the TSCs exclusively. Thus, the clinical goal of a
donor lymphocyte drugs, the remission of tumor-stem-
tumorigenic) as well as against healthy cells of the breast
therapy, which excludes the possibility of non-responders
cell-derived tumors in humanized SCID mice models can
parenchyma from the outer area of the tumor.
or of relapses, is now available. Such technology for the
be effectively carried out. At the Fraunhofer Institute for
development of a bio-medical innovation as well as a
Cell Therapy and Immunology TSC-specic CD8+ donor
cell-therapeutic product, generated from isolated and
lymphocyte drugs can be produced in GMP conditions
characteristic tumor stem cells of diverse tumor identities,
and applied clinically as cell therapeutic drugs in order to
which can be introduced on the market (hospitals)
treat solid malignant tumors.
directly, has thus far been realized in Germany only by the
Fraunhofer Institute.
Fraunhofer IZI Service Catalog | IZI360-02
FRAUNHOFER INSTITUTE FOR CELL THERAPY AND IMMUNOLOGY
CYTOSTATIC DRUGS AND CELL THERAPEUTIC DRUGS SCREENING ASSAYS /
IN VIVO TESTING IN MOUSE MODEL
FOLLOWING TUMOR INDUCTION
Prole of the Fraunhofer IZI
Tumor Stem Cells Group
The Fraunhofer Institute for Immunology and Cell Therapy
Our group focuses on the identication, isolation, characterization,
IZI founded in April 2005 is member of the Fraunhofer
and expansion of undifferentiated tumor stem cells from various
Life Sciences Alliance. Its objective being to nd solutions
tumor entities. One initial focus is the testing of new innovative
to specic problems at the interfaces between medicine,
cytostatic drugs as a scientic-commercial service. Our scientic
life sciences and engineering for partners active in
work centers on nding prospective specically targeted medica-
medicine-related industries and businesses. The Institute’s
tions as well as cell-based interventions aimed at various tumor
core competencies are to be found in regenerative
specic tumor stem cells.
medicine, or more precisely in cell-therapeutic methods of
regenerating non-functioning tissue and organs through
to the biological substitution with tissue cultivated in vitro
(tissue engineering). In order for the living organism to
accept the tissues without any difculty, it is necessary
to study cellular and immunological defense and control
mechanisms and take these into account during process
and product development. These core competencies
entail a multiplicity of tasks to be solved by new products
and processes. The Institute works especially closely with
hospital institutions, performing quality tests and clinical
studies on their behalf. Additionally it also provides
assistance in obtaining manufacturing licenses and
certications.
Fraunhofer-Institut für
Zelltherapie und Immunologie
Contact
Director
Dr. Peter Ruschpler
Prof. Dr. Frank Emmrich
Tumor Stem Cells Group
Perlickstr. 1
Phone: +49 (0) 341 / 355 36-2605
04103 Leipzig
[email protected]
Germany
Phone:
+49 (0) 341 / 355 36-1000
Fax :
+49 (0) 341 / 355 36-9921
[email protected]
PN: IZI360-03
www.izi.fraunhofer.de
© Fraunhofer IZI, status: 04/2009
tumor induction
CYTOSTATIC DRUGS AND CELL THERAPEUTIC DRUGS SCREENING ASSAYS /
IN VIVO TESTING IN MOUSE MODEL
FOLLOWING TUMOR INDUCTION
Tumor stem cells (TSCs) are ascribed a signicant role
intervention against tumor
novel active agents / TSC specic CD8+ CTL
TSC
Unique Feature
Selected Applications
possess the typical stem cell characteristics, such as self
The tumor stem cells which are applied at the Fraunhofer
Using this application, IND candidates and / or cell thera-
derived CD8+ T lymphocytes
renewal and differentiation potential. At the present time
Institute for Cell Therapy and Immunology are unique.
peutic drugs can be tested in vivo on tumors derived from
and / or novel active agents.
it is assumed that this type of cell is resistant to various
Using humanized mice, exclusive tumorigenesis and
TSCs – as a supplement to in vitro testing (IZI360-1) – in
forms of therapy and that it leads both to relapses and to
unique chimerism analyses have become possible which
humanized and wild-type mice regarding their cytostatic /
metastases.
enable a precise distinction between CD8+-CTL-transplant
cytotoxic potential.
Tumor induction via TSC and
in the development of various forms of cancer. They
tumor intervention by TSC
Further Products & Services of this Group
(human) and the receptor (mouse model).
At the Fraunhofer Institute for Cell Therapy and
Immunology an in vivo model system has been developed
which enables a rapid and practice-oriented investigation
Reference Project
–
of multiple investigational new drug (IND) candidates
At the Fraunhofer Institute for Cell Therapy and Immuno-
which inhibit tumor stem cell lines. A tumor was induced
First of all, tumor stem cells of various entities are applied
logy the therapeutic inuence of new stem cell fractions
by applying TSCs in an established mouse model. IND
in a humanized mouse model in order to commence TSC-
on the reconstitution of hematopoiesis in humanized mice
candidates and / or cell therapeutic drugs against TSCs
initiated tumorigenesis. Intervention using IND candidates
was investigated more precisely in an independent research
are infused and their therapeutic effect is assessed in
and cell therapeutic agents on these TSCs in the animal
project. The repair potential of these cells on various organs
the course of clinical and laboratory diagnoses as well as
enables the previously conducted in vitro testing to be
and tissues was characterized.
through post-mortem histological examinations.
expanded qualitatively and represents a new therapeutic
–
Personalized Tumor Killer-Cells (IZI360-02)
Associated Products & Services at the Institute
–
Cell Tracking (IZI310-02)
–
Diagnosis and Therapy Model (Mouse) of Salmonellosis
(Salmonella enterica) (IZI120-07)
category. The experimental read out for therapy success
can be carried out via laboratory diagnostics in the course
Cytostatic Drugs / In Vitro Testing of Tumor Stem Cells
for Various Solid Malignant Tumors (IZI360-01)
Methods
–
GMP Manufacturing of Cell Based Medicinal Products
and Tissue Preparations (IZI110-01)
of the procedure as well as post-mortem and comprises
the identication of peripheral blood parameters (FACS
–
GvHD-Model in Mice (IZI220-03)
and CBA) as well as histological, immunohistological and
–
Non-coding RNA Biomarkers for Oncological Diseases,
nONCOchip (IZI520-02)
molecular biological processes. The reprocessing of the
residual tumor into an individual suspension is an essential
–
Supplements and Biomaterials (IZI330-05)
assessment factor with respect to the occurrence of TSCs
(FACS, real-time-PCR).
(Stem Cell) Cytotoxicity of Additives, Compounds,
–
Therapeutic Mouse Model: A Human Immune System
for Testing of Active Ingredients (IZI130-02)
Fraunhofer IZI Service Catalog | IZI360-03
FRAUNHOFER INSTITUTE FOR CELL THERAPY AND IMMUNOLOGY
DEFENSINS AND
ANTIMICROBIAL PEPTIDES
Prole of the Fraunhofer IZI
Vascular Biology Group
The Fraunhofer Institute for Immunology and Cell Therapy
The goal of this group is the development of a preventative and
IZI founded in April 2005 is member of the Fraunhofer
at least partially curative gene therapy for arthrosclerosis. Using
Life Sciences Alliance. Its objective being to nd solutions
vascular models, genes and promoters are identied that can
to specic problems at the interfaces between medicine,
be activated by biomechanical forces such as ow or stretching.
life sciences and engineering for partners active in
Because cardiovascular disease is often induced by dental disease
medicine-related industries and businesses. The Institute’s
(caries, periodontitis), a second focus of the group is in the
core competencies are to be found in regenerative
establishment of a therapy against oral streptococcus.
medicine, or more precisely in cell-therapeutic methods of
regenerating non-functioning tissue and organs through
to the biological substitution with tissue cultivated in vitro
(tissue engineering). In order for the living organism to
accept the tissues without any difculty, it is necessary
to study cellular and immunological defense and control
mechanisms and take these into account during process
and product development. These core competencies
entail a multiplicity of tasks to be solved by new products
and processes. The Institute works especially closely with
hospital institutions, performing quality tests and clinical
studies on their behalf. Additionally it also provides
assistance in obtaining manufacturing licenses and
certications.
Fraunhofer-Institut für
Zelltherapie und Immunologie
Contact
Director
Dr. Andreas Schubert
Prof. Dr. Frank Emmrich
Vascular Biology Group
Perlickstr. 1
Phone: +49 (0) 341 / 355 36-5105
04103 Leipzig
[email protected]
Germany
Phone:
+49 (0) 341 / 355 36-1000
Fax :
+49 (0) 341 / 355 36-9921
[email protected]
PN: IZI510-01
www.izi.fraunhofer.de
© Fraunhofer IZI, status: 04/2009
DEFENSINS AND
ANTIMICROBIAL PEPTIDES
The treatment of infectious diseases is one of the
Client Advantage
Selected Applications
Further Products & Services of this Group
Microorganisms have developed numerous resistances as
A plasmid library which covers a range of several billion
–
–
a result of inappropriate use of antibiotics. Against this
different antimicrobial peptides has been established at
background, many antibiotics can no longer be used.
Fraunhofer IZI. This plasmid library can be used to test the
Peptide-antibiotics will play a leading role as an alternative
effect of codied antimicrobial peptides in a co-culture
treatment to the current antibiotics in the near future.
against one or more human pathogenic bacteria. A great
These substances have the capacity to treat virtually every
advantage of the predominantly small antimicrobial
infectious disease effectively.
peptides lies in their marginal immunogenicity.
greatest challenges facing modern medicine today.
development of therapies against antibiotic resistant
development of functional food additives
Associated Products & Services at the Institute
Reference Project
The antimicrobial effect of different peptides on the main
The Fraunhofer IZI follows an alternative approach to
close this gap. Mutational variations of peptides are
(pathogenic) organism for the development of tooth decay,
Methods
being developed on the basis of known sequence motifs
Arteriosclerosis / Dental Plaque (IZI510-02)
infectious diseases
–
Assay System for Isolation of Biomarkers in
–
Microarray Analysis (IZI520-06)
–
Screening for Compounds with Antiviral Activity
(IZI250-03)
Streptococcus mutans, has been tested in a project at the
Fraunhofer IZI. In the process, many antimicrobial peptides
and being tested on different human pathogenic germs.
The cloning of know and modied sequence motifs in
that stunt the growth and reproduction of Streptococcus
Through the modication of only those peptides which
combination is carried out in specic expression-plasmids
mutans have been identied.
are antimicrobially effective only the pathogenic bacteria
which can cultivated in E. coli. Following this step, a
are killed and the commensal ora is not negatively
co-culture system is created in which E. coli and another
affected. There is a possibility of creating an antimicrobial
pathogenic bacterium under investigation are cultivated
peptide library for client-specic application.
to a level that both germs can tolerate.. Plasmids are
isolated from the E. coli colonies, which are surrounded
by growth inhibiting aureoles and then sequenced. The
stability and cytotoxicity of the peptides within in the
human alimentary canal are subsequently tested in cell
culture models.
Fraunhofer IZI Service Catalog | IZI510-01
FRAUNHOFER INSTITUTE FOR CELL THERAPY AND IMMUNOLOGY
ASSAY SYSTEM FOR ISOLATION OF
BIOMARKERS IN ARTERIOSCLEROSIS /
DENTAL PLAQUE
Prole of the Fraunhofer IZI
Vascular Biology Group
The Fraunhofer Institute for Immunology and Cell Therapy
The goal of this group is the development of a preventative and
IZI founded in April 2005 is member of the Fraunhofer
at least partially curative gene therapy for arthrosclerosis. Using
Life Sciences Alliance. Its objective being to nd solutions
vascular models, genes and promoters are identied that can
to specic problems at the interfaces between medicine,
be activated by biomechanical forces such as ow or stretching.
life sciences and engineering for partners active in
Because cardiovascular disease is often induced by dental disease
medicine-related industries and businesses. The Institute’s
(caries, periodontitis), a second focus of the group is in the
core competencies are to be found in regenerative
establishment of a therapy against oral streptococcus.
medicine, or more precisely in cell-therapeutic methods of
regenerating non-functioning tissue and organs through
to the biological substitution with tissue cultivated in vitro
(tissue engineering). In order for the living organism to
accept the tissues without any difculty, it is necessary
to study cellular and immunological defense and control
mechanisms and take these into account during process
and product development. These core competencies
entail a multiplicity of tasks to be solved by new products
and processes. The Institute works especially closely with
hospital institutions, performing quality tests and clinical
studies on their behalf. Additionally it also provides
assistance in obtaining manufacturing licenses and
certications.
Fraunhofer-Institut für
Zelltherapie und Immunologie
Contact
Director
Dr. Andreas Schubert
Prof. Dr. Frank Emmrich
Vascular Biology Group
Perlickstr. 1
Phone: +49 (0) 341 / 355 36-5105
04103 Leipzig
[email protected]
Germany
Phone:
+49 (0) 341 / 355 36-1000
Fax :
+49 (0) 341 / 355 36-9921
[email protected]
PN: IZI510-02
www.izi.fraunhofer.de
© Fraunhofer IZI, status: 04/2009
ASSAY SYSTEM FOR ISOLATION OF
BIOMARKERS IN ARTERIOSCLEROSIS /
DENTAL PLAQUE
The emergence of arteriosclerosis is closely associated
Unique Feature
Selected Applications
Further Products & Services of this Group
During the process of atherogenesis, the ow prole
The BTF system is based on ow generation with the
Using the ow equipment, anti-arteriosclerotic substances
–
inuencing the endothelial cells plays a critical role. With
cone-plate-method. This specically constructed system
and drugs can be tested on endothelial cultures under
the aid of the BioTechFlow-System (BTF) it is possible to
is uniquely designed. Through the cone-geometry, the
dened ow conditions. Furthermore, RNA, membrane
simulate in vitro the in vivo predominant ow conditions
system is capable to generate an array of ow proles,
fractions and proteins can be assayed under specic ow
which are very close to reality. These ow conditions can
and therefore can simulate in vivo conditions precisely.
conditions.
lead to multiple changes within the cells (e.g. alterations
The BTF system represents a level of technology which
in mRNA expression, protein expression and composition
allows examination of owinduced cell differentiation, in
of the cellmembrane), which may constitute possible
various cell types including endothelial cells, tumor cells
points of eventual therapy for arteriosclerosis.
and stem cells. A signicant advantage of the BTF system
with dened ow conditions within the vascular system.
Animal Model Systems for Cardiac Ischemia –
Rat / Mouse (IZI320-07)
Reference Project
–
Diagnosis and Therapy Model (Mouse) of Salmonellosis
(Salmonella enterica) (IZI120-07)
in comparison to other ow systems is that the cells can
Under application of the BTF system several genes, which
be continuously observed with the microscope during
had been selectively activated through a pro-atherogene
exposed to very clearly dened ow proles with the
ow application.
ow prole have already been identied. Furthermore,
–
Therapeutic Mouse Model: A Human Immune System
for Testing of Active Ingredients (IZI130-02)
–
Nanometer Pathogen-Sieb (IZI250-04)
the promoter sequences of those genes have been more
genes and signal transduction pathways in cells, which
primarily contribute to the emergence of “arteriosclerosis-
Associated Products & Services at the Institute
–
Human or animal cells (e.g. endothelial cells) can be
help of BTF. It is therefore possible to identify the target
Defensins and Antimicrobial Peptides (IZI510-01)
accurately analyzed. In the process transcription factor
Methods
endangered” endothelial phenotypes.
binding-sites have been identied, through which the gene
activation may take place.
The cells under investigation will be cultivated on a substrate and upon reaching a conuency of approximately
70 percent they are exposed to a dened ow prole.
Subsequently, the preparation of RNA, proteins or
membrane is carried out for further analysis. Additionally,
immunohistochemical investigations of the cells can be
carried out on the substrate.
Fraunhofer IZI Service Catalog | IZI510-02
FRAUNHOFER INSTITUTE FOR CELL THERAPY AND IMMUNOLOGY
NON-CODING RNA BIOMARKERS
Prole of the Fraunhofer IZI
RNomics Group
The Fraunhofer Institute for Immunology and Cell Therapy
The RNomics Group identies and characterizes disease-associated
IZI founded in April 2005 is member of the Fraunhofer
nonprotein coding RNAs (ncRNAs) for the development of novel
Life Sciences Alliance. Its objective being to nd solutions
diagnostic markers and therapeutic targets. The group develops
to specic problems at the interfaces between medicine,
experimental and bioinformatic methods for this task with a special
life sciences and engineering for partners active in
focus on applicability in disease and system-independent models as
medicine-related industries and businesses. The Institute’s
well as general use.
core competencies are to be found in regenerative
medicine, or more precisely in cell-therapeutic methods of
regenerating non-functioning tissue and organs through
to the biological substitution with tissue cultivated in vitro
(tissue engineering). In order for the living organism to
accept the tissues without any difculty, it is necessary
to study cellular and immunological defense and control
mechanisms and take these into account during process
and product development. These core competencies
entail a multiplicity of tasks to be solved by new products
and processes. The Institute works especially closely with
hospital institutions, performing quality tests and clinical
studies on their behalf. Additionally it also provides
assistance in obtaining manufacturing licenses and
certications.
Fraunhofer-Institut für
Zelltherapie und Immunologie
Contact
Director
Dr. Jörg Hackermüller
Prof. Dr. Frank Emmrich
RNomics Group
Perlickstr. 1
Phone: +49 (0) 341 / 355 36-5205
04103 Leipzig
[email protected]
Germany
Phone:
+49 (0) 341 / 355 36-1000
Fax :
+49 (0) 341 / 355 36-9921
[email protected]
PN: IZI520-01
www.izi.fraunhofer.de
© Fraunhofer IZI, status: 04/2009
NON-CODING RNA BIOMARKERS
Only about 1.5 percent of the 3.3 billion bases of the
Unique Feature
To continue a study with less material and experimental
–
The ENCODE consortium (2007). Identication and
effort after an initial genome wide phase for identication
analysis of functional elements in 1% of the human
shown that the predominant, non-protein coding part
Due to their extremely precise regulation, depending on
of ncRNA candidates, we have several custom microarray
genome by the ENCODE pilot project. Nature 447: 799
of the genome is actively transcribed into RNA as well.
factors like cellular state, tissue type or disease, ncRNAs
platforms available. With the nONCOchip, we have
Generation of these non-protein coding RNAs (ncRNAs)
represent a novel class of potent biomarker candidates.
developed a microarray for oncological questions,
is highly specically regulated and ncRNAs are disease-
Additionally, because of the relative novelty of the
which covers numerous ncRNAs that are regulated by
associated in a lot of cases. A human cell has the ability
research area and the large number of ncRNAs, this topic
oncologically relevant signalling pathways. All microarray
to generate a considerably larger number of different
offers a broad freedom-to-operate. Despite of their short
techniques are automated in essential processing steps, to
ENCODE Selected Regions of the Human Genome.
ncRNAs compared to mRNAs and many more ncRNAs
history, some established ncRNA biomarkers already
guarantee a higher reproducibility, throughput and fewer
Genome Res. 17: 852
are cell type or condition specic. NcRNAs are therefore
exist, for example PCA3 in clinical diagnostics of prostate
labor costs.
promising biomarker candidates. Although individual
carcinoma or miRNAs for the characterization of stem cell
ncRNAs are used as biomarkers in clinical diagnostics,
populations and their differentiation processes.
human genome code for proteins. In recent studies it was
they are typically not included in systematic studies for the
development of new biomarkers.
–
Kapranov et al. (2007). Genome-wide RNA Maps
Reveal New RNA Classes and a Possible Function
for Pervasive Transcription. Science, 316: 1484
–
–
Washietl et al. (2007). Structured RNAs in the
Löfer et al. (2007). Interleukin-6-dependent survival
of multiple myeloma cells involves the Stat3-
For validation of biomarkers in larger cohorts we can
mediated induction of micro RNA-21 through a
achieve high throughput by using pipetting robots and
highly conserved enhancer. Blood. 110:1330-3
As ncRNA biomarker studies also include the characteriza-
high throughput RT-PCR machines. These methods and
tion and quantication of unknown transcripts, they are
processes are also offered for mRNA expression studies.
Further Products & Services of this Group
Fraunhofer IZI offers a wide palette of customer services
always of a certain complexity, which requires an excellent
and products for the development of ncRNA based
link between study design, experimental procedure
biomarkers. Biomarkers for oncological diseases are
and bioinformatic analysis. The latter is of particular
developed within in-house research projects (IZI520-02).
importance, as genome-wide studies like those needed
Services include expression analysis of known ncRNAs
for the identication of novel ncRNAs, lead to huge and
Development of biomarkers based on the expression of
–
Non-coding RNAs as Therapeutic Targets (IZI520-03)
– e.g. micro RNAs – in medium and high throughput, as
complex data sets. Fraunhofer IZI links experimental
non-protein coding RNA for diagnostics, clinical substudies
–
Transcriptome Analysis Using Tiling Arrays and
well as methods and strategies for the identication of
and bioinformatic competencies within one group and
and control of therapy response, as well as characterization
novel ncRNAs. The latter is relevant in particular, as most
is therefore well prepared for such challenges. This is
and identication of specic stem cell populations, for
ncRNAs have not yet been characterized and thus an ex-
also proved by the participation in several international
example in stem cell or tumor stem cell research.
cellent IP situation for ncRNA biomarkers exists. With the
networking research projects, like the ENCODE project
nONCOchip, we offer a tool for biomarker identication
that were of importance for understanding the biological
for oncological questions that allows the identication
relevance of ncRNAs.
Selected Applications
Non-coding RNA Biomarkers for Oncological Diseases,
nONCOchip (IZI520-02)
Ultra-high-throughput Sequencing (IZI520-04)
–
micro RNA Analysis (Expression, Localization, Targets)
(IZI520-05)
–
Microarray Analysis (IZI520-06)
Reference Project
Associated Products & Services at the Institute
of a large number of oncologically relevant ncRNAs that
were experimentally identied in our group, besides those
already known.
–
Fraunhofer IZI has been an active partner in international
Methods
research projects that were of extreme importance for the
understanding of the relevance and extent of transcrip-
Depending on the demands of the project partners it is
Novel ncRNAs are identied via genome wide tiling arrays
tion of non-coding parts of the genome (see selected
possible to perform complete biomarker studies, as well
or high throughput sequencing. Thus, the simultaneous
publications). In several internal transcriptomic projects
as specic aspects of such studies, like expression analysis
identication and quantication of already known, as
new ncRNAs were identied that were regulated by
or bioinformatics and statistics.
well as novel ncRNAs in the analyzed samples is possible.
disease relevant signalling pathways. Amongst others we
For analysis of the complex data sets a high performance
succeeded in identifying ncRNAs, which have the capability
computing cluster is available, using published and in-
to characterize specic stages of prostate carcinoma.
–
Cytostatic Drugs / In Vitro Testing of Tumor Stem Cells
for Various Solid Malignant Tumors (IZI360-01)
house developed bioinformatic methods.
Fraunhofer IZI Service Catalog | IZI520-01
FRAUNHOFER INSTITUTE FOR CELL THERAPY AND IMMUNOLOGY
NON-CODING RNA BIOMARKERS FOR
ONCOLOGICAL DISEASES, nONCOchip
Prole of the Fraunhofer IZI
RNomics Group
The Fraunhofer Institute for Immunology and Cell Therapy
The RNomics Group identies and characterizes disease-associated
IZI founded in April 2005 is member of the Fraunhofer
nonprotein coding RNAs (ncRNAs) for the development of novel
Life Sciences Alliance. Its objective being to nd solutions
diagnostic markers and therapeutic targets. The group develops
to specic problems at the interfaces between medicine,
experimental and bioinformatic methods for this task with a special
life sciences and engineering for partners active in
focus on applicability in disease and system-independent models as
medicine-related industries and businesses. The Institute’s
well as general use.
core competencies are to be found in regenerative
medicine, or more precisely in cell-therapeutic methods of
regenerating non-functioning tissue and organs through
to the biological substitution with tissue cultivated in vitro
(tissue engineering). In order for the living organism to
accept the tissues without any difculty, it is necessary
to study cellular and immunological defense and control
mechanisms and take these into account during process
and product development. These core competencies
entail a multiplicity of tasks to be solved by new products
and processes. The Institute works especially closely with
hospital institutions, performing quality tests and clinical
studies on their behalf. Additionally it also provides
assistance in obtaining manufacturing licenses and
certications.
Fraunhofer-Institut für
Zelltherapie und Immunologie
Contact
Director
Dr. Jörg Hackermüller
Prof. Dr. Frank Emmrich
RNomics Group
Perlickstr. 1
Phone: +49 (0) 341 / 355 36-5205
04103 Leipzig
[email protected]
Germany
Phone:
+49 (0) 341 / 355 36-1000
Fax :
+49 (0) 341 / 355 36-9921
[email protected]
PN: IZI520-02
www.izi.fraunhofer.de
© Fraunhofer IZI, status: 04/2009
NON-CODING RNA BIOMARKERS FOR
ONCOLOGICAL DISEASES, nONCOchip
is important, as genome-wide studies to nd novel ncRNAs
from healthy patients and are qualied as biomarkers.
produce large and complex data sets. The ability of Fraun-
Using tiling array analysis in a cell culture model, we
hofer IZI in this area has already been demonstrated, as we
could identify ncRNA candidates, which showed strong
participated in international networking research projects
overexpression in the late tumor stage; those results could
as the ENCODE project, which was extremely important for
be veried in patient samples. The Fraunhofer IZI can offer
the appreciation of the relevance of ncRNAs.
a potential marker for recurrent PCa. Our experiences with
transcriptomic projects are reected in several publications
with international partners:
Methods
–
The ENCODE consortium (2007). Identication and
analysis of functional elements in 1% of the
Novel ncRNAs will be identied via genome-wide tiling-
human genome by the ENCODE pilot project.
array analysis or high throughput sequencing. Thus, the
Nature 447: 799
The term non-coding RNA, describes the part of the large
Depending on the customer’s needs Fraunhofer IZI
concomitant identication and quantication of known
transcriptome that does not code for proteins. The huge
conducts complete biomarker studies, but also performs
as well as novel ncRNAs is possible. For the analysis of the
Reveal New RNA Classes and a Possible Function
potential of oncological biomarkers has already been
several aspects like expression analysis, bioinformatics or
resulting complex data sets a high performance computing
for Pervasive Transcription. Science, 316: 1484
demonstrated, e.g., the expression of the ncRNA PCA3 is
statistics in the context of large studies.
cluster is available and both published and in-house
used in clinical prostate cancer diagnosis. The importance
–
–
designed bioinformatical methods are applied.
Löfer et al. (2007). Interleukin-6-dependent survival
of multiple myeloma cells involves the Stat3-
of many ncRNAs – particularly micro RNAs – during
tumorigenesis is well established. The ENCODE project,
Kapranov et al. (2007). Genome-wide RNA Maps
mediated induction of micro RNA-21 through a
Unique Feature
in which the Fraunhofer IZI participated, showed that
Several custom microarray platforms are available to con-
highly conserved enhancer. Blood, May 11
tinue a study after an initial genome-wide phase to identify
the bulk of the 33 billion bases of the human genome
NcRNAs are a novel class of potent biomarker candidates
ncRNA candidates at a more material and cost effective
is transcribed into RNA, whereas only 1.5 percent code
as their expression is highly specically regulated depend-
level. The nONCOchip is a custom array, tailor-made to
for proteins (ENCODE project consortium, Nature 2007).
ent on cellular state, type of tissue and diseases. Due to
answer oncological problems. All microarray processes have
Further Products & Services of this Group
Therefore the freedom to operate in this scientic eld is
the short history of this research eld and the enormous
been automated where possible and feasible to ensure high
–
Non-coding RNA Biomarkers (IZI520-01)
extraordinarily high. NcRNAs form promising biomarker
number of detected ncRNAs so far, the freedom to
reproducibility, throughput and to lower labor costs.
–
Non-coding RNAs as Therapeutic Targets (IZI520-03)
candidates, as the number of ncRNAs produced in a
operate is wide.
–
Transcriptome Analysis Using Tiling Arrays and
For the validation of biomarkers in big cohorts and to gain
human cell is much higher than the number of messenger
RNAs and they are expressed in a highly controlled, cell
The nONCOchip, a product specically developed for
high throughput the Fraunhofer IZI uses pipetting robots
type and state specic manner.
oncological diseases, detects a multiplicity of novel, so
and high throughput RT-PCR devices.
far undescribed and tumor-relevant ncRNAs, which were
Ultra-high-throughput Sequencing (IZI520-04)
–
(IZI520-05)
–
The Fraunhofer IZI provides many services and products
detected in elaborate experiments. The nONCOchip
to develop ncRNA biomarkers for oncological diseases.
includes multiple tumor-relevant signaling pathways –
This includes strategies and methods for the identication
therefore it can be employed to analyze a broad range of
of novel and uncharacterized ncRNAs as well as the
tumor diseases. For those diseases, the nONCOchip is able
Development of biomarkers based on the expression
quantication of known ncRNAs.
to replace cost intensive and time consuming genome-
of ncRNAs to solve oncological problems, especially for
micro RNA Analysis (Expression, Localization, Targets)
Microarray Analysis (IZI520-06)
Selected Applications
Associated Products & Services at the Institute
wide experiments to identify novel ncRNAs. Hence, the
diagnostic use, clinical trials, controls in therapy progression
With the nONCOchip, the Fraunhofer IZI provides
nONCOchip enables customers to perform efcient and
as well as characterization and identication of specic cell
an effective tool for the development of biomarkers,
cost-effective non-coding RNA biomarker studies in the
populations, e.g. tumor stem cell research.
which has been attuned to oncological questions. The
oncological research area.
–
Bioluminescence and Fluorescence Imaging for
–
Customized Development and Validation of Immuno-
Preclinical In Vivo Small Animal Studies (IZI310-01)
logical In Vitro Test Systems (IZI120-04)
–
nONCOchip detects 240 000 RNA signals, besides known
Cytostatic Drugs and Cell Therapeutic Drugs Screening
Assays / In Vivo Testing in Mouse Model Following
and bioinformatically predicted RNAs, the chip interro-
Fraunhofer IZI combines experimental, bioinformatical and
gates experimentally detected tumor-relevant ncRNAs.
statistical competencies in one workgroup. Thereby, ex-
The latter are ncRNAs that are regulated in the context of
perimental aspects as well as data analysis and processing
There is a high demand on biomarkers for diagnosing ag-
tumor-relevant signalling pathways like p53, STAT3 and
within a study can be covered. This is extremely relevant
gressive forms of prostate cancer (PCa). micro RNA (miRNA)
in the cell cycle. They have been experimentally detected
for genome-wide ncRNA biomarker studies, which include
expression studies in a cell culture model and in clinical
at Fraunhofer IZI and are predominantly undescribed.
the characterization and quantication of unknown
samples helped to identify several miRNAs, which are lost in
Additionally, the nONCOchip includes ncRNAs which were
transcripts. Those studies include a certain level of
PCa; in the meantime, a causal role in tumorigenesis could
differentially expressed in solid tumor and healthy tissue
complexity assuming superior interconnection of strategy
be assigned. By contrast we could not identify miRNAs that
samples.
and experimental and bioinformatical analysis. The latter
showed higher expression in PCa compared to samples
Reference Project
Tumor Induction (IZI360-03)
Fraunhofer IZI Service Catalog | IZI520-02
FRAUNHOFER INSTITUTE FOR CELL THERAPY AND IMMUNOLOGY
NON-CODING RNAS AS
THERAPEUTIC TARGETS
Prole of the Fraunhofer IZI
RNomics Group
The Fraunhofer Institute for Immunology and Cell Therapy
The RNomics Group identies and characterizes disease-associated
IZI founded in April 2005 is member of the Fraunhofer
nonprotein coding RNAs (ncRNAs) for the development of novel
Life Sciences Alliance. Its objective being to nd solutions
diagnostic markers and therapeutic targets. The group develops
to specic problems at the interfaces between medicine,
experimental and bioinformatic methods for this task with a special
life sciences and engineering for partners active in
focus on applicability in disease and system-independent models as
medicine-related industries and businesses. The Institute’s
well as general use.
core competencies are to be found in regenerative
medicine, or more precisely in cell-therapeutic methods of
regenerating non-functioning tissue and organs through
to the biological substitution with tissue cultivated in vitro
(tissue engineering). In order for the living organism to
accept the tissues without any difculty, it is necessary
to study cellular and immunological defense and control
mechanisms and take these into account during process
and product development. These core competencies
entail a multiplicity of tasks to be solved by new products
and processes. The Institute works especially closely with
hospital institutions, performing quality tests and clinical
studies on their behalf. Additionally it also provides
assistance in obtaining manufacturing licenses and
certications.
Fraunhofer-Institut für
Zelltherapie und Immunologie
Contact
Director
Dr. Jörg Hackermüller
Prof. Dr. Frank Emmrich
RNomics Group
Perlickstr. 1
Phone: +49 (0) 341 / 355 36-5205
04103 Leipzig
[email protected]
Germany
Phone:
+49 (0) 341 / 355 36-1000
Fax :
+49 (0) 341 / 355 36-9921
[email protected]
PN: IZI520-03
www.izi.fraunhofer.de
© Fraunhofer IZI, status: 04/2009
NON-CODING RNAS AS
THERAPEUTIC TARGETS
Methods
Reference Project
Further Products & Services of this Group
the cells. Meanwhile, compelling evidence suggests that
In the context of national and international collaborations
Within genome-wide transcriptome projects, like the
–
Non-coding RNA Biomarkers (IZI520-01)
besides mRNAs the much larger and so far inadequately
and projects, the Fraunhofer IZI tries to understand the
ENCODE project (The ENCODE project consortium, Nature
–
Non-coding RNA Biomarkers for Oncological Diseases,
characterized class of non-protein coding RNAs (ncRNAs),
functions of ncRNAs and make them applicable for
2007) or in collaboration with Affymetrix (Kapranov et
has a key role in pathological processes.
biomarker and therapeutic purposes. We develop and
al, Science, 2007), high numbers of ncRNAs have been
improve strategies to disable the respective ncRNA. For
identied. Efcient bioinformatic selection methods have
So far, the analysis of such transcripts in the context of
this use we combine bioinformatic and experimental
been applied and enhanced to determine which ncRNAs
different diseases is not adequately exploited to develop
processes, e.g. to predict the most efcient knock-down
can be characterized experimentally (e.g. J Exp Zoolog B
novel therapeutic targets, although the huge freedom to
method before realizing it experimentally. We also
Mol Dev Evol, 2007).
operate associated with these transcripts is very attractive
develop techniques to articially insert or produce one
for the pharmaceutical industry as well as clinical research.
particular ncRNA in certain cellular systems, similar to
Those procedures have been applied to in-house transcrip-
the overexpression of protein-coding genes. Subsequent
tome datasets measured in different pathophysiological
Identied disease-associated ncRNAs will be reduced to a
to overexpression or knock-down, physiological effects
states. Numerous potential targets could be identied
set of candidate drug targets via bioinformatical methods
like increased or decreased apoptosis or proliferation,
and will be validated as therapeutic targets using specic
with regard to the customer’s needs. Those candidates
invasiveness or modications in the protein prole, which
inhibitors.
will be specically manipulated and affected by means of
were caused by this manipulation, will be analyzed.
A large number of abnormal states in cells and organisms
arise from the aberrant production of RNA transcripts in
nONCOchip (IZI520-02)
–
Transcriptome Analysis Using Tiling Arrays and
Ultra-high-throughput Sequencing (IZI520-04)
–
micro RNA Analysis (Expression, Localization, Targets)
(IZI520-05)
–
Microarray Analysis (IZI520-06)
Associated Products & Services at the Institute
–
Developmental Toxicity of Additives, Compounds,
Supplements and Biomaterials (IZI330-04)
–
GLP Studies – Differential Proteomics (Available 2009)
(IZI120-09)
established methods, like RNA interference, ribozymes or
aptameres in a sequence and structure specic way. The
Fraunhofer IZI offers a broad characterization of identied
Selected Applications
targets and their manipulation in cell culture models and
in in vivo models. The analysis of direct and secondary
Identication and validation of novel therapeutic targets
effects caused by those manipulations will help to validate
based on ncRNAs and the development of novel strategies
ncRNA candidates as targets; strategies for manipulation
for therapy in the eld of oncology, neurology and
can be developed and provided.
infectious diseases.
Unique Feature
One class of ncRNAs, the micro RNAs, are particularly in
the focus of research and many potential targets were
identied in this class in recent years and several are
meanwhile in clinical testing. However, an inexhaustible
number of other non-coding transcripts besides micro
RNAs exist and their interference with fundamental molecular processes has already been demonstrated; therefore
their exploitation as therapeutic targets is conceivable.
Fraunhofer IZI Service Catalog | IZI520-03
FRAUNHOFER INSTITUTE FOR CELL THERAPY AND IMMUNOLOGY
TRANSCRIPTOME ANALYSIS USING
TILING ARRAYS AND ULTRA-HIGHTHROUGHPUT SEQUENCING
Prole of the Fraunhofer IZI
RNomics Group
The Fraunhofer Institute for Immunology and Cell Therapy
The RNomics Group identies and characterizes disease-associated
IZI founded in April 2005 is member of the Fraunhofer
nonprotein coding RNAs (ncRNAs) for the development of novel
Life Sciences Alliance. Its objective being to nd solutions
diagnostic markers and therapeutic targets. The group develops
to specic problems at the interfaces between medicine,
experimental and bioinformatic methods for this task with a special
life sciences and engineering for partners active in
focus on applicability in disease and system-independent models as
medicine-related industries and businesses. The Institute’s
well as general use.
core competencies are to be found in regenerative
medicine, or more precisely in cell-therapeutic methods of
regenerating non-functioning tissue and organs through
to the biological substitution with tissue cultivated in vitro
(tissue engineering). In order for the living organism to
accept the tissues without any difculty, it is necessary
to study cellular and immunological defense and control
mechanisms and take these into account during process
and product development. These core competencies
entail a multiplicity of tasks to be solved by new products
and processes. The Institute works especially closely with
hospital institutions, performing quality tests and clinical
studies on their behalf. Additionally it also provides
assistance in obtaining manufacturing licenses and
certications.
Fraunhofer-Institut für
Zelltherapie und Immunologie
Contact
Director
Dr. Jörg Hackermüller
Prof. Dr. Frank Emmrich
RNomics Group
Perlickstr. 1
Phone: +49 (0) 341 / 355 36-5205
04103 Leipzig
[email protected]
Germany
Phone:
+49 (0) 341 / 355 36-1000
Fax :
+49 (0) 341 / 355 36-9921
[email protected]
PN: IZI520-04
www.izi.fraunhofer.de
© Fraunhofer IZI, status: 04/2009
TRANSCRIPTOME ANALYSIS USING
TILING ARRAYS AND ULTRA-HIGHTHROUGHPUT SEQUENCING
The set of all RNAs in a cell in a certain state is dened as
The experimental detection of the transcriptional activity
The amount of data produced by those high-throughput
Selected Publications:
its transcriptome. Although a human cell can produce sig-
of the whole genome is complex and generates a large
methods necessitates the development of innovative bio-
–
nicantly more ncRNA than mRNA transcipts, the analysis
amount of data, which requires experience in bioinforma-
informatical methods for data analysis. This is done at the
of transcriptomes in most cases is restricted to mRNAs.
tics for the analysis. Such studies can only be performed
Fraunhofer IZI in close cooperation with the Interdisciplinary
This analysis is misleading as ncRNAs are regulated more
by a few and specialized centres. The RNomics Group at
Center for Bioinformatics at the University of Leipzig. Our
stringently in contrast to mRNAs, and therefore theses
the Fraunhofer IZI has been arranged to this challenge
services for these methods cover the whole process – from
ENCODE Selected Regions of the Human Genome.
molecules are preeminently applicable as biomarkers.
from the beginning and provides a strong connection
RNA isolation to processing, labelling, quality control,
Genome Res. 17: 852
The majority of non-protein coding transcripts are so far
between experimenters and bioinformaticians in one
hybridization and scanning of the tiling arrays up to
not characterized and hence offer an enormous freedom
working group. The group also cooperates closely with
sequencing and data analysis. Follow-up experiments for
of multiple myeloma cells involves the Stat3-
to operate on the one hand and on the other hand
the Interdisciplinary Center for Bioinformatics at the
the validation or the development of custom microarrays,
mediated induction of micro RNA-21 through a
require methods that detect known and novel transcripts
University of Leipzig. Successful projects for the characteri-
which only cover the highly interesting parts detected
highly conserved enhancer. Blood, May 11
similarly. For these questions, the Fraunhofer IZI uses
zation of novel ncRNA biomarkers in prostate cancer as
during genome-wide analysis, can also be performed at the
genome-wide tiling arrays and ultra-high-throughput
well as the participation on several international research
Fraunhofer IZI.
sequencing.
projects prove the ability of the Fraunhofer IZI.
Kapranov et al. (2007). Genome-wide RNA Maps
Reveal New RNA Classes and a Possible Function
for Pervasive Transcription. Science, 316: 1484
–
–
Washietl et al. (2007). Structured RNAs in the
Löfer et al. (2007). Interleukin-6-dependent survival
Further Products & Services of this Group
The Fraunhofer IZI offers comprehensive analyses of
the transcriptomes of different cellular systems and
Selected Applications
Methods
organisms (e.g. human, mice, Drosophila melanogaster
The identication of novel biomarkers for diagnostic use,
–
Non-coding RNA Biomarkers (IZI520-01)
–
Non-coding RNA Biomarkers for Oncological Diseases,
nONCOchip (IZI520-02)
and bacteria). The analysis may contain transcripts of the
As the main part of ncRNA is uncharacterized so far, there
sub-studies and control of therapy response as well as
whole genome (non-repetitive part), but also be based
is a need for methods that are useful to efciently and
research on recent therapeutic approaches on the basis of
–
Non-coding RNAs as Therapeutic Targets (IZI520-03)
on selected regions and therefore be highly customer
simultaneously identify and quantify unknown and known
ncRNAs.
–
micro RNA Analysis (Expression, Localization, Targets)
oriented. Our services include experimental procedures as
RNAs. Currently two techniques full these needs –
well as professional and customized analyses of generated
genome-wide tiling arrays and transcriptome sequencing
complex data sets.
with ultra-high-throughput. Tiling arrays expand the
(IZI520-05)
–
Microarray Analysis (IZI520-06)
Reference Project
known principle of microarrays, as they screen the whole
Unique Feature
genome (non-repetitive) using probes. Tiling arrays are
In close international cooperation we were able to show
well suited for the detection of transcripts longer than
the biological relevance of analyzing the human transcrip-
Associated Products & Services at the Institute
100nt. Ultra-high-throughput sequencing detects the
tome and a multiplicity of novel transcripts, with inuence
–
Highly Complex cDNA Libraries (IZI250-02)
The search for novel biomarkers is primarily performed
sequences of a high number of transcripts and quanties
on cellular physiology, were identied (see selected
–
SNP Analysis in Human Genome (IZI320-06)
on proteins or protein-coding genes. However, only 1.5
a certain sequence via counting. Besides the detection of
publications). At the Fraunhofer IZI those methods were
percent of the human genome code for proteins. Recent
ncRNAs, both techniques can be used for the classication
used to identify new biomarkers and therapeutic targets for
studies, in which the Fraunhofer IZI participated, have
of protein-DNA-interactions (ChIP-on-ChIP) or the
oncology.
demonstrated that the remaining 98 percent of the
localization of epigenetic modications, like methylation
genome are transcribed actively and highly specically
and acetylation.
into RNA (e.g. Encode project consortium, Nature 2007).
As those non-protein coding transcripts are often associated with diseases, their acquisition is highly relevant for
biomedical research.
Fraunhofer IZI Service Catalog | IZI520-04
FRAUNHOFER INSTITUTE FOR CELL THERAPY AND IMMUNOLOGY
MICRO RNA ANALYSIS (EXPRESSION,
LOCALIZATION, TARGETS)
Prole of the Fraunhofer IZI
RNomics Group
The Fraunhofer Institute for Immunology and Cell Therapy
The RNomics Group identies and characterizes disease-associated
IZI founded in April 2005 is member of the Fraunhofer
nonprotein coding RNAs (ncRNAs) for the development of novel
Life Sciences Alliance. Its objective being to nd solutions
diagnostic markers and therapeutic targets. The group develops
to specic problems at the interfaces between medicine,
experimental and bioinformatic methods for this task with a special
life sciences and engineering for partners active in
focus on applicability in disease and system-independent models as
medicine-related industries and businesses. The Institute’s
well as general use.
core competencies are to be found in regenerative
medicine, or more precisely in cell-therapeutic methods of
regenerating non-functioning tissue and organs through
to the biological substitution with tissue cultivated in vitro
(tissue engineering). In order for the living organism to
accept the tissues without any difculty, it is necessary
to study cellular and immunological defense and control
mechanisms and take these into account during process
and product development. These core competencies
entail a multiplicity of tasks to be solved by new products
and processes. The Institute works especially closely with
hospital institutions, performing quality tests and clinical
studies on their behalf. Additionally it also provides
assistance in obtaining manufacturing licenses and
certications.
Fraunhofer-Institut für
Zelltherapie und Immunologie
Contact
Director
Dr. Jörg Hackermüller
Prof. Dr. Frank Emmrich
RNomics Group
Perlickstr. 1
Phone: +49 (0) 341 / 355 36-5205
04103 Leipzig
[email protected]
Germany
Phone:
+49 (0) 341 / 355 36-1000
Fax :
+49 (0) 341 / 355 36-9921
[email protected]
PN: IZI520-05
www.izi.fraunhofer.de
© Fraunhofer IZI, status: 04/2009
MICRO RNA ANALYSIS (EXPRESSION,
LOCALIZATION, TARGETS)
Unique Feature
Selected Applications
Further Products & Services of this Group
cellular processes. To date, a large number of micro RNAs
The expression and functional analysis of micro RNAs in
Analysis of expression of micro RNAs in cellular systems
–
Non-coding RNA Biomarkers (IZI520-01)
are known that are involved in pathological processes like
different pathological conditions opens up completely
of diverse species, disease and developmental stages, cell
–
Non-coding RNA Biomarkers for Oncological Diseases,
metabolic and psychiatric diseases, infections and also
new perspectives for the identication and development
physiological characterization of micro RNA transcripts,
in cancer. Some micro RNAs have been identied to be
of biomarkers and therapeutic targets based on the cell
micro RNAs in signalling pathways, analysis of micro RNA
–
Non-coding RNAs as Therapeutic Targets (IZI520-03)
the main regulators and modulators of cell physiological
type, disease, and developmental specic expression of
targets, creation of regulatory networks.
–
Transcriptome Analysis Using Tiling Arrays and
processes – cell growth, proliferation, and apoptosis.
this molecule class.
micro RNAs are small, ~20nt long non-protein coding
RNA molecules that play essential roles in fundamental
nONCOchip (IZI520-02)
Ultra-high-throughput Sequencing (IZI520-04)
–
Additionally, it was demonstrated that micro RNAs
are highly specically regulated and expressed within
Through the close linking and bundling of biological,
disease and developmental stages. Based on the specic
experimental and bioinformatic competencies, Fraunhofer
expression and their causative relation with diseases,
IZI is a one-stop shop for the complete procedure of
A comprehensive study of micro RNAs in prostate carci-
micro RNAs represent a new class of biomarkers and
expression and functionality studies of micro RNAs.
noma led to the identication of a large number of tumor
Microarray Analysis (IZI520-06)
Reference Project
Associated Products & Services at the Institute
potential therapeutic targets and establish a new eld of
specic micro RNAs and the verication of their expression
–
Cell Transduction (IZI250-05)
therapeutic applications.
in clinical material. Hereby a signicant differential expres-
–
GLP Studies – Differential Proteomics (Available 2009)
Methods
(IZI120-09)
sion of different patient groups could be shown.
–
Fraunhofer IZI offers customer specic solutions for the
expression analysis of micro RNA genes in tissues and
The identication of micro RNAs is based on microarray
In a cooperative project with scientists of the University of
cells, e.g. for identication of diagnostic and prognostic
or quantitative PCR techniques. Thereby analysis of all
Leipzig, micro RNAs could be identied which are involved
biomarkers that allow the discrimination of different
known micro RNAs is offered. Another, more compre-
in the development of a hematopoetical cancer (multiple
progression stages or subtypes of a disease and subpopu-
hensive possibility of the expression analysis is ultra-
myeloma). In particular, one micro RNA was identied
lations of patients.
high-throughput sequencing, where the identication
which inhibits the controlled cell death of tumor cells
of yet undescribed micro RNAs (and other small RNAs) is
(Löfer et al., Blood, 2007). At the moment, this micro RNA
Furthermore, the services comprise the manipulation of
possible. Depending on the chosen method a compre-
is being further functionally characterized, with the aim of
cellular systems for the analysis of physiological effects of
hensive bioinformatic analysis is carried out according to
determining its applicability as a therapeutic target.
micro RNA, as well as the identication and validation of
the customer’s requirements.
micro RNA targets and determination of the subcellular
Reprogramming of Cells – iPS (induced Pluripotent
Stem Cells) (IZI340-02)
In other collaborations with academic partners and industry
localization of micro RNAs with the help of bioinformatic
micro RNAs that have been identied to be differentially
partners, micro RNA expression studies of diverse organisms
and experimental methods.
regulated in a particular cellular system or organism are
and cellular systems have been carried out.
analyzed with respect to their relevance and function
using different methods. Thereby we determine the
physiological role (for example, parameters like apoptosis,
proliferation or invasiveness of the cells in tumor biology),
identify and validate potential micro RNA targets via
different approaches of bioinformatics, genomics or
proteomics, and analyze the signalling pathways which
are regulated by or regulate the micro RNA.
Fraunhofer IZI Service Catalog | IZI520-05
FRAUNHOFER INSTITUTE FOR CELL THERAPY AND IMMUNOLOGY
MICROARRAY ANALYSIS
Prole of the Fraunhofer IZI
RNomics Group
The Fraunhofer Institute for Immunology and Cell Therapy
The RNomics Group identies and characterizes disease-associated
IZI founded in April 2005 is member of the Fraunhofer
nonprotein coding RNAs (ncRNAs) for the development of novel
Life Sciences Alliance. Its objective being to nd solutions
diagnostic markers and therapeutic targets. The group develops
to specic problems at the interfaces between medicine,
experimental and bioinformatic methods for this task with a special
life sciences and engineering for partners active in
focus on applicability in disease and system-independent models as
medicine-related industries and businesses. The Institute’s
well as general use.
core competencies are to be found in regenerative
medicine, or more precisely in cell-therapeutic methods of
regenerating non-functioning tissue and organs through
to the biological substitution with tissue cultivated in vitro
(tissue engineering). In order for the living organism to
accept the tissues without any difculty, it is necessary
to study cellular and immunological defense and control
mechanisms and take these into account during process
and product development. These core competencies
entail a multiplicity of tasks to be solved by new products
and processes. The Institute works especially closely with
hospital institutions, performing quality tests and clinical
studies on their behalf. Additionally it also provides
assistance in obtaining manufacturing licenses and
certications.
Fraunhofer-Institut für
Zelltherapie und Immunologie
Contact
Director
Dr. Jörg Hackermüller
Prof. Dr. Frank Emmrich
RNomics Group
Perlickstr. 1
Phone: +49 (0) 341 / 355 36-5205
04103 Leipzig
[email protected]
Germany
Phone:
+49 (0) 341 / 355 36-1000
Fax :
+49 (0) 341 / 355 36-9921
[email protected]
PN: IZI520-06
www.izi.fraunhofer.de
© Fraunhofer IZI, status: 04/2009
MICROARRAY ANALYSIS
Selected Applications
Further Products & Services of this Group
data analysis and the design of microarrays that t the
Analysis of gene expression (mRNA, exons), gene poly-
–
Non-coding RNA Biomarkers (IZI520-01)
expression in studies for the investigation and diagnosis of
aims of the customer. Quality control and reproducibility
morphisms (SNPs), mircoRNA, non-coding transcripts, as
–
Non-coding RNA Biomarkers for Oncological Diseases,
diseases (e.g. tumor diseases, infections, neurological di-
of the analyses have top priority.
well as the development of customer specic microarrays.
Fraunhofer IZI conducts microarray analyses for the
The close interconnection of experimental biology and
pharmaceutical industry, biotech and academic institu-
bioinformatics at Fraunhofer IZI allows for comprehensive
tions. Thereby we aim at the analysis of differential gene
seases) to facilitate the development of novel diagnostics,
as well as new therapeutic targets.
The demand for genome wide detection of transcripts
requires laborious array experiments, which in turn require
nONCOchip (IZI520-02)
–
Non-coding RNAs as Therapeutic Targets (IZI520-03)
–
Transcriptome Analysis Using Tiling Arrays and Ultrahigh-throughput Sequencing (IZI520-04)
Reference Project
–
Other elds of application are determining disease sub-
highly automated processing to enable a high throughput.
types, analyzing treatment response, as well as screening
Fraunhofer IZI is perfectly equipped for large expression
In collaboration with partners from different research
pharmaceutical agents.
studies with several hundred arrays.
facilities, gene expression and transcriptome analyses
micro RNA Analysis (Expression, Localization, Targets)
(IZI520-05)
of diverse cellular systems have been performed. This
included the analysis of signalling pathways in tumor cells
Unique Feature
Methods
Associated Products & Services at the Institute
or immunological and infectiological questions in which
mRNA as well as ncRNA (e.g., miRNA) expression analyses
–
Highly Complex cDNA Libraries (IZI250-02)
were performed.
–
Cytostatic Drugs / In Vitro Testing of Tumor Stem Cells
In the recent decade microarray technologies emerged as
As an Affymetrix® service provider Fraunhofer IZI offers
one of the most important and widespread technologies
all varieties of array studies based on Affymetrix® arrays –
in biological and biomedical research and the pharma-
starting with the sample preparation to the hybridization
–
Defensins and Antimicrobial Peptides (IZI510-01)
ceutical industry. The intrinsic principles of microarrays –
and data analysis. Additionally, equipment for efcient
–
Screening for Compounds with Antiviral Activity
miniaturization, automation and parallelization – allow a
quality control is available, e.g. an Agilent Bioanalyzer sys-
considerable increase in the throughput of simultaneously
tem. Furthermore, we can specically design microarrays
measurable parameters. Fraunhofer IZI is conducting
together with the customer, tailoring the arrays to the
microarray analyses using arrays of several manufacturers
particular eld of application. Bioinformatic analysis of the
allowing a selection of products that are optimal for the
generated data is carried out according to the customer’s
customer’s need.
specic requirements.
for Various Solid Malignant Tumors (IZI360-01)
(IZI250-03)
–
SNP Analysis in Human Genome (IZI320-06)
Fraunhofer IZI Service Catalog | IZI520-06
FRAUNHOFER INSTITUTE FOR CELL THERAPY AND IMMUNOLOGY
ARTHRITIS MODEL IN THE MOUSE
Prole of the Fraunhofer IZI
Molecular Diagnostics Group
The Fraunhofer Institute for Immunology and Cell Therapy
Our team develops rapid and easy-to-handle systems for the
IZI founded in April 2005 is member of the Fraunhofer
analysis and modelling of immunological and genetic processes
Life Sciences Alliance. Its objective being to nd solutions
in the elds of transplantation, inammation research, and tumor
to specic problems at the interfaces between medicine,
biology. Our main foci are articular and lung diseases, which are
life sciences and engineering for partners active in
investigated through the application of novel immunoassays,
medicine-related industries and businesses. The Institute’s
genetic analyses, complex cell culture models, and animal experi-
core competencies are to be found in regenerative
ments.
medicine, or more precisely in cell-therapeutic methods of
regenerating non-functioning tissue and organs through
to the biological substitution with tissue cultivated in vitro
(tissue engineering). In order for the living organism to
accept the tissues without any difculty, it is necessary
to study cellular and immunological defense and control
mechanisms and take these into account during process
and product development. These core competencies
entail a multiplicity of tasks to be solved by new products
and processes. The Institute works especially closely with
hospital institutions, performing quality tests and clinical
studies on their behalf. Additionally it also provides
assistance in obtaining manufacturing licenses and
certications.
Fraunhofer-Institut für
Zelltherapie und Immunologie
Contact
Director
Prof. Dr. Ulrich Sack
Prof. Dr. Frank Emmrich
Molecular Diagnostics Group
Perlickstr. 1
Phone: +49 (0) 341 / 97 25-506
04103 Leipzig
[email protected]
Germany
Phone:
+49 (0) 341 / 355 36-1000
Fax :
+49 (0) 341 / 355 36-9921
[email protected]
PN: IZI530-01
www.izi.fraunhofer.de
© Fraunhofer IZI, status: 04/2009
ARTHRITIS MODEL IN THE MOUSE
To test new treatment strategies for joint inammation,
Methods
Reference Projects
Further Products & Services of this Group
–
collagen induced arthritis, antibody induced arthritis,
–
broblast induced joint destruction in the mouse
–
Cartilage Destruction Model in the Mouse (IZI530-02)
–
Cellular Function Test for Tissue-destructive Fibroblasts
models must unite immunological, inammatory, acute /
chronic and / or destructive aspects of human disease
according to the specic principles of each disease. At
broblast induced arthritis
–
stem cell therapy of joint destruction
Fraunhofer IZI, a specic selection of animal models are
–
imaging diagnostics in the mouse
–
examination of granulocyte directed therapies
available for exploring and studying joint inammation
–
serological multiplex analyses
–
examination of antibodies in arthritis therapy
and cartilage destruction. One may choose immunization
–
ow cytometric cell analysis
using different antigens, a communication of arthritogenic
–
gene expression analysis
antibodies or the transfer of destructive broblasts.
–
metabolic screening
–
histology, immunohistochemistry
(IZI530-03)
Associated Products & Services at the Institute
–
GvHD-Model in Mice (IZI220-03)
–
Rat Model of Focal Cerebral Ischemia (Stroke)
(IZI320-02)
Unique Feature
Selected Applications
The diversity of arthritis models available at Fraunhofer IZI
is unique and allows for an extensive spectrum of testing.
–
testing new therapeutic processes
–
demonstrate efcacy of medicaments for arthritis
–
Stem Cell Media Formulations (IZI330-03)
–
Therapeutic Mouse Model: A Human Immune System
for Testing of Active Ingredients (IZI130-02)
–
Client Advantage
–
illustration of the effect mechanism of novel
–
–
clarication of dosage and application type
expected effects and type of mechanism being tested.
–
examination of tolerance and side effects
–
examination of innovative combination therapies
Therapy Models (Mouse) of Chronic-inammatory
Bowel Diseases (IZI120-06)
therapeutic principles
Flexible development of a custom model according to
Therapy Model for Tissue Regeneration (Fractures)
(IZI330-01)
therapy
–
Three-dimensional Stem Cell Cultures Bone / Cartilage –
Mechanical Training (IZI330-02)
Fraunhofer IZI Service Catalog | IZI530-01
FRAUNHOFER INSTITUTE FOR CELL THERAPY AND IMMUNOLOGY
CARTILAGE DESTRUCTION MODEL
IN THE MOUSE
Prole of the Fraunhofer IZI
Molecular Diagnostics Group
The Fraunhofer Institute for Immunology and Cell Therapy
Our team develops rapid and easy-to-handle systems for the
IZI founded in April 2005 is member of the Fraunhofer
analysis and modelling of immunological and genetic processes
Life Sciences Alliance. Its objective being to nd solutions
in the elds of transplantation, inammation research, and tumor
to specic problems at the interfaces between medicine,
biology. Our main foci are articular and lung diseases, which are
life sciences and engineering for partners active in
investigated through the application of novel immunoassays,
medicine-related industries and businesses. The Institute’s
genetic analyses, complex cell culture models, and animal experi-
core competencies are to be found in regenerative
ments.
medicine, or more precisely in cell-therapeutic methods of
regenerating non-functioning tissue and organs through
to the biological substitution with tissue cultivated in vitro
(tissue engineering). In order for the living organism to
accept the tissues without any difculty, it is necessary
to study cellular and immunological defense and control
mechanisms and take these into account during process
and product development. These core competencies
entail a multiplicity of tasks to be solved by new products
and processes. The Institute works especially closely with
hospital institutions, performing quality tests and clinical
studies on their behalf. Additionally it also provides
assistance in obtaining manufacturing licenses and
certications.
Fraunhofer-Institut für
Zelltherapie und Immunologie
Contact
Director
Prof. Dr. Ulrich Sack
Prof. Dr. Frank Emmrich
Molecular Diagnostics Group
Perlickstr. 1
Phone: +49 (0) 341 / 97 25-506
04103 Leipzig
[email protected]
Germany
Phone:
+49 (0) 341 / 355 36-1000
Fax :
+49 (0) 341 / 355 36-9921
[email protected]
PN: IZI530-02
www.izi.fraunhofer.de
© Fraunhofer IZI, status: 04/2009
CARTILAGE DESTRUCTION MODEL
IN THE MOUSE
Chronic joint destruction is the main challenge for
Methods
Reference Projects
Further Products & Services of this Group
To meet this challenge, models are required that mirror,
–
broblast induced arthritis
–
broblast induced joint destruction in the mouse
–
Arthritis Model in the Mouse (IZI530-01)
in particular, the destructive aspects of human disease.
–
imaging diagnostics in the mouse
–
stem cell therapy of joint destruction
–
Cellular Function Test for Tissue-destructive Fibroblasts
At Fraunhofer IZI, two models in immune decient SCID
–
serological multiplex analyses
–
examination of antibodies in arthritis therapy
mice are available specially to explore questions centering
–
gene expression analysis
around cartilage destruction. To this end, destructive
–
metabolic screening
broblasts of human or murine origin are used.
–
histology, immunohistochemistry
Unique Feature
Selected Applications
–
GvHD-Model in Mice (IZI220-03)
The diversity of arthritis models available at Fraunhofer IZI
–
testing new therapeutic processes
–
Ovine Large Animal Model of Stroke (IZI320-03)
is unique and allows for an extensive spectrum of testing.
–
demonstrate efcacy of medicaments for arthritis
–
Proof of Biocompatibility and Risk Analysis (IZI130-01)
therapy
–
Three-dimensional Stem Cell Cultures Bone / Cartilage –
researchers of new treatment strategies in rheumatology.
(IZI530-03)
Associated Products & Services at the Institute
–
–
Client Advantage
illustration of the effect mechanism of novel
Diagnosis and Therapy Model (Mouse) of Borreliosis
(Borrelia burgdorferi) (IZI120-08)
Mechanical Training (IZI330-02)
therapeutic principles
–
clarication of dosage and application type
Flexible development of a custom model according to
–
examination of tolerance and side effects
expected effects and type of mechanism being tested
–
examination of innovative combination therapies
Fraunhofer IZI Service Catalog | IZI530-02
FRAUNHOFER INSTITUTE FOR CELL THERAPY AND IMMUNOLOGY
CELLULAR FUNCTION TEST FOR
TISSUE-DESTRUCTIVE FIBROBLASTS
Prole of the Fraunhofer IZI
Molecular Diagnostics Group
The Fraunhofer Institute for Immunology and Cell Therapy
Our team develops rapid and easy-to-handle systems for the
IZI founded in April 2005 is member of the Fraunhofer
analysis and modelling of immunological and genetic processes
Life Sciences Alliance. Its objective being to nd solutions
in the elds of transplantation, inammation research, and tumor
to specic problems at the interfaces between medicine,
biology. Our main foci are articular and lung diseases, which are
life sciences and engineering for partners active in
investigated through the application of novel immunoassays,
medicine-related industries and businesses. The Institute’s
genetic analyses, complex cell culture models, and animal experi-
core competencies are to be found in regenerative
ments.
medicine, or more precisely in cell-therapeutic methods of
regenerating non-functioning tissue and organs through
to the biological substitution with tissue cultivated in vitro
(tissue engineering). In order for the living organism to
accept the tissues without any difculty, it is necessary
to study cellular and immunological defense and control
mechanisms and take these into account during process
and product development. These core competencies
entail a multiplicity of tasks to be solved by new products
and processes. The Institute works especially closely with
hospital institutions, performing quality tests and clinical
studies on their behalf. Additionally it also provides
assistance in obtaining manufacturing licenses and
certications.
Fraunhofer-Institut für
Zelltherapie und Immunologie
Contact
Director
Prof. Dr. Ulrich Sack
Prof. Dr. Frank Emmrich
Molecular Diagnostics Group
Perlickstr. 1
Phone: +49 (0) 341 / 97 25-506
04103 Leipzig
[email protected]
Germany
Phone:
+49 (0) 341 / 355 36-1000
Fax :
+49 (0) 341 / 355 36-9921
[email protected]
PN: IZI530-03
www.izi.fraunhofer.de
© Fraunhofer IZI, status: 04/2009
CELLULAR FUNCTION TEST FOR
TISSUE-DESTRUCTIVE FIBROBLASTS
Methods
Reference Project
Further Products & Services of this Group
To meet this challenge, models are required that mirror,
–
broblast induced arthritis
Examination of antibodies in arthritis therapy
–
Arthritis Model in the Mouse (IZI530-01)
in particular, the destructive aspects of human disease. At
–
serological multiplex analyses
–
Cartilage Destruction Model in the Mouse (IZI530-02)
Fraunhofer IZI, two in vitro models have been developed
–
gene expression analysis
on the basis of isolated destructive broblasts. These
–
automated microscopy
Chronic joint destruction is the main challenge for
researchers of new treatment strategies in rheumatology.
Associated Products & Services at the Institute
models allow the targeted exploration of questions about
cartilage destruction. To this end, destructive broblasts of
human or murine origin are used.
Unique Feature
Selected Applications
–
testing new therapeutic processes
–
demonstrate efcacy of medicaments for arthritis
–
Cell Transduction (IZI250-05)
–
Conditioned Humanized / Non Humanized Mouse
Model (IZI220-01)
–
This in vitro joint destruction model is unique and
–
exclusively available at Fraunhofer IZI.
–
Developmental Toxicity of Additives, Compounds,
Supplements and Biomaterials (IZI330-04)
therapy
illustration of the effect mechanism of novel
–
Humanized, Triple Transgenic Mouse (IZI220-02)
therapeutic principles
–
Proof of Biocompatibility and Risk Analysis (IZI130-01)
examination of innovative combination therapies
Fraunhofer IZI Service Catalog | IZI530-03
gel electrophoresis: Method to separate molecules
(e. g. DNA, proteins) by the migration of electrically
loaded particles within a gel
i.m. (intramuscular): Applied into the muscle
genome: The entirity of the genes within a cell
i.v. (intravenous): Applied into the vein
genotoxicity: Effect of chemical substances that causes
pathological changes in the genome
ICH: International Conference on Harmonisation of Technical
Requirements for Registration of Pharmaceuticals for Human Use
genotyping: Preparation of a genetic ngerprint,
characterization of certain sections of the genome
Ig / immunoglobulin / antibody: Proteins, produced by the
immune system as reaction against foreign material or cells
(antigenes)
i.p. (intraperitoneal): Applied into the abdominal cavity
F R A U N H O F E R - I N S T I T U T F Ü R Z E L LT H E R A P I E U N D I M M U N O L O G I E
gliagenesis: Formation of glia cells (specialized nerve
cells)
GLOSSARY (A - L)
GLP (Good Laboratory Practice): Quality management for non clinical, health relevant and environmental
relevant safety tests, including planning, realization and
contolling, documentation, archiving and reporting of
investigations carried out in laboratory
glycoprotein: Proteins with one or more covalent
bounded carbohydrate groups
GMP (Good Manufacturing Practice): Guidlines for the
quality management of manufacturing processes and surrounding for the production of drugs, active agents and
medical devices as well as food and animal foodstuffs
IL 8 / Interleukin 8: Messenger protein produced naturally in the
body, inammation mediator
immunodecient: Unable to develop a immological response
immunoassay: Method to detect a substance based of a antigenantibody reactionen
immunoblot: Method to detect proteins, transfered to a carrier
membrane (plotting) and detected by different immunological
reactions
immunotoxicity: Effect of chemical substances, causes pathogen
changes of the immune system
immunosuppresiv: To repress a immunological reaction
Graft-versus-Host-Disease (GvHD): Immunological
reaction of a transplant including immunocompetent cells
against an immune supressed host
in vitro: Outside of a living organism
in vivo: Inside of a living organism
hematopoetic: Blood forming
HLA-Molecules (human leukocyte antigens): A cell
surface molecules responible for immunological
recognition and immune tolerance (histocompatibility) in
transplantation
hybridoma: Fusion product of an antibody producing
cell (B cell) with an myeloma cell (B-lymphocyte-cancer
cell); has the nature of immortality and rapid proliferation,
is able to produce a specic kind of anti bodies over a
various time
hypertension / hypertensive: Increased pressure (e. g.
blood pressure)
hypoxia: Oxygen deciency
induced pluriputent stem cells (iPS): Articial reprogrammed
somatic cells, transfered to an embryonic state
interleukins: Messenger molecules (e. g. peptides) of immune
cells
ischemia: Undersupply of tissue or organs with oxygen
lenti viruses: Genus within the family of retro viruses; cause
slowly (lentus = slow ) progressive, degenerative diseases
LIF (Leukemia-inhibiting factor): Cell product, inhibits the
proliferation of leukemia cells
Lipopolysaccharid: Compound of fat like (lipo) and sugar
components (polysaccharid); located in the outside membrane
of gram negative bacteria
© Fraunhofer IZI, Stand: 04/2009
GLOSSARY (A - L)
acetylation: Chemical modication of proteins by a
acetyl group, affects the biological function
array: Parallel analysis of many single detections in a
analysing device
adhesion: Mechanically cohesion between substances,
caused by molecular interactions
assay: Test / detection of certain substances
autologous: Derived from one´s own body
cell adhesion molecules: Proteins that provide contact
between cells within tissue
defensins: Small peptides present in all animal and plant
organisms, serve the defences of microbial pathogens
cell migration: Migration of cells within a organism
cell transduction: Introducing genes into a cell
dendritic cells: Immune cells; serve the antigen
presentation and affect the specic cellular immune
defence
cerebral: Belongs to the brain
drug delivery: Controlled release of active agents
chondrogen: Cartilage forming
electrophoresis: Method to separate molecules (e. g.
DNA, proteins) by the migration of electrical loaded
particles within a substrate
chromatographie: separation of a mixture of substances
based on the different allocation of the several properties
between an stationary and a mobile phase
cloning: Molecular biological method to amplify DNA,
therefore a DNA-fragment is transfered into a host cell
(e. g. bacteria) by a vector (e. g. plasmid), the DNAfragment will proliferate as the host cell proliferates
ELISA (enzyme linked immunosorbent assay):
Immunological method based on enzymatic reaction
embryonal stem cells: Stem cells that are able to differentiate into every kind of cell type (pluripotent), present
only in the embryonal-development stage (blastocyst)
adipogen: Fat-building
adult stem cells: Stem cells able to differntiate into
different kind of cells of certain tissues; are present in
many organs of the adult organism
afnity: Tendency of atoms to interact (binding strength)
bioluminescence: The ability of organisms to generate
light
bioluminescent imaging: Imaging based on faint
glowing markers, detected in vivo and generated by
genetically integrated enzymes
CNP (copy number polymorphism): Variation of the
number of copies of an certain DNA section within a
genom
EMEA: European Medicines Agency
epigenetic modication: Chemical modication of the
DNA, without changes in the sequence (e. g. methylation)
CNS: Central nervous system
erythrocytes: Red blood cells; serve oxygen transport
colon: Part of the large intestine
aliquot: Seperate into equal volumes
allogen: Descend from a different organism of the same
species
biomarker: Meansurable molecules, useful to indicate
diseases
biotin: Water soluble vitamin of the B-complex, useful for
marking different kind of molecules
comet assay: Method to detect DNA damages in single
cells
ex vivo: Outside of the living organism
cardiomyocytes: Heart muscle cells
commensal ora: Total common germs located on or in
the body (e. g. oral cavity, intestinal tract, skin), partly with
physical function
antigen: Immunological response releasing structure
(e. g. proteins or carbohydrates on the cell surface or in
dilution)
carrier proteins: Proteins that active transports
molecules through cell membranes
conjugation (of antibodies): Connection of antibodies
with other molecules (e. g. enzymes)
anti body / immunoglobuline: Proteins produced by the
immune systeme in answer to impurities / cells (antigenes),
binds the antigen
CD4: CD4 (cluster of differentation 4) is a glycoprotein, on
the surface of immune cells (helper T-cells, monocytes and
macrophages)
CT (Computer-Tomography): Medical imaging method,
assembles radiograms taken from different directions to a
three-dimensional picture
anti serum: Serum of immunized organisms
CD4+ T-cells: Immune cells (T-lymphocytes) with CD4molecules (cluster of differentation 4) on the surface,
mostly helper T-cells
cryopreservation: Storing of cells, tissue and organs under
extremely low temperatures (e. g. within liquid nitrogen)
amplication: Augmentation (e. g. DNA sections)
apoptosis: Controlled cell death
cytokine: Messenger molecules released by cells
aptamers: Short, single strand DNA or RNA molecules,
bind specic molecules (e. g. growth factors, toxins)
cDNA (complementary DNA): DNA, established by
transcription of a mRNA (messenger RNA); this activity is
catalyzed by the enzyme reverse transcriptase
evaluation: Is the description, analysis and estimation of
processes and experimental models
FACS (uorescence activated cell sorting): Flow cytomic
cell sorting, cell characterization
FDA: Food and Drug Administration
broblasts: Cells of the connective tissue, contribute to
the extracellular matrix by providing collagen
FITC: Fluoresceinisothiocyanat, uorescent dye
focal: Comes from the disease center
GCP (good clinical practice): International accepted guidlines for the performance of clinical trials, in consideration
of medical, ethical and scientic aspects
cytotoxic: Causing cell death
Fraunhofer IZI-Leistungskatalog | IZI110-01
F R A U N H O F E R - I N S T I T U T F Ü R Z E L LT H E R A P I E U N D I M M U N O L O G I E
STAIR criteria: STAIR (Stroke Therapy Academic Industry
Roundtable) is a consortium of scientists and industry that
published recommendations for the preclinical and clinical
development of neuroprotective therapies
TSC (Tumor Stem Cells): Tumor cells with stem cell
characteristics (self renewal and potenzial to differentiate)
STAT3: Intra cellular protein, has functions within the
molecular signaling of cells
validation: Demonstration of a thesis; validation provides a documented evidence for the specic functionality of processes, active
agents or equipment among practical tems
T-cell synapse: Biochemical signal cascade to activate T-cells
telomere: Single strand ending of chromosomes
vasogenesis: Formation of blood vessels
telomerase: Enzym in the cell nucleus with the function
of a reverse transcriptase, rebuilds segments of the telomers that were lost during cell division
vector: Carrier
verication: Proof of a assumption
GLOSSARY (M - Z)
teratogenicity : Embryotoxic; attribute of a substance to
generate deformities with in the embryonal development
thrombocyte: Blood plates (part of the blood clotting
system)
vitrication: Freezing of a uid by cooling
western blot: See immunoblot
xenogen: Derived from an other species
Tilling (targeting induced local lesions in genomes)Array: Method to identify mutations within certain genes,
array means the parallel analysis of several thousands
single detections in less volume of a biological sample
xenotransplantation: Transfer of fully functional
cells ore tissue (including organs and parts of the body)
between different species
TNF (Tumor-Necrosis-Factor): Messenger of the immune
system; inammation mediator
transgen: Genes introduced in another genome
transient: Temporary
transcription: Biochemical process, DNA-segments are
transcribed into RNA; the synthesis of the RNA takes place
on the basis of a DNA original
transcription factor: Proteins of the cell core with
impact on the initiation of the transcription
Treg: Regulatory T-cells; originally suppressor T-cells;
specic T-cells that protect the organism from overreaction
and provide self tolerance; dyfunction causes allergies and
autoimmune reactions
© Fraunhofer IZI, Stand: 04/2009
pathogen: Microorganisms or molecules that causes diseases in a organism
GLOSSARY (M - Z)
preclinical trials: Studies during the development of active
agents to test the biological safety and pharmacokinetic,
tests are conducted at suitable models
pathogenesis: Development and progress of an disease
progenitor: Precursor
PCR: Polymerase chain reaction, molecular biological method to amplify DNA-segments
PE: Phycoerythrin (uorescence dye)
MALDI-TOF: Method for large quantity analysing of
chemical compound; MALDI: Matrix Assisted Laser
Desorption / Ionisation; TOF: Time Of Flight
multiple myeloma: Cancer disease of the bone marrow;
characterized by malignant prolifaration of antibodyforming plasma cells
mesenchymal stem cells: Progenitor cells of the
connective tissue
native proteins: Natural, unmodied proteins
PEG-Fusion: Fusion of cells inuenced by the chemical
substance polyethylenglycol (PEG)
PET (positron emission tomography): Medical imaging
method, displays biochemical and physiological functions,
detects low radioactive labeled compounds in the body
phagocytes: Immune cells that assimilate living or lifeless
particles
proliferation: Cell and tissue growth
Proof-of-Principle-trial: Study that demonstrats the
concept in principle
proteom: Total of all proteins in a organism (cell) at a
selected time and under dened terms
proteomics: Exploration of the proteom – i. e. the total of
all proteins present in a cell at a dened time under dened
terms
R&D: Research and Development
phagocytosis: Active assimilation of particles by a cell
methylation: Chemical modication of the DNA
by methyl groups, with different biological functions
(e. g. protection of the DNA)
ncRNA (non coding RNA): RNA molecules that does not
encode proteins; partly with regulating function within
the cell
methylcellulose: Chemical compound, becomes semiuid (gel) in cold water; thickening agent, emulsier
necrosis: Uncontrolled cell death
pharmacokinetics: Total processes that active agents
underlie in the organism
REACH: EU-regulation for Registration, Evaluation,
Authorisation and Restriction of Chemicals
recombinant: Genetically engineered (e. g. proteins)
MHC-molecules (Major Histocompatibility Complex):
Encompasses a group of cell surface molecules important
for the immunological identication and tissue compatibility (histo compatibility), important for transplantations
and immunological individuality
microRNA: Short ribonucleic acid (RNA)-molecules with
important functions in the gen regualtion
monoclonal anti bodies: Antibodies, produced by one
single B-lymphocyte clone
needle inoculation: Inserting substances by a needle
(e. g. vaccines)
NK-cells: Natural killer cells; immune cells without specic
antigen receptor, are able to detect and destroy virus
infected cells and abnormal cells like tumor cells
Non-Responder: Patient who does not react on
therapeutic aproaches
osteogen: Bone forming
MTT Assay: Method to demonstrate cell vitality with the
dye 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
bromide (MTT)
recombinant proteins: In genetically engineered microorganisms produced proteins
Phase II (clinical trial): Clinical trial of a drug in human
regarding to therapeutic effectivity
relapse: Re-occurance of a disease
Phase III (clinical trial): Clinical trial of a drug in human to
proof the effectivity in large scale, mulicenter investigated
patient groups with the goal of admission to the market
retrovirus: Reverse transcriptase including viruses, the
genetic information exist as RNA is transcibed into DNA
and integrated into the genome of the host cell
phenotype: Appearance
ribozyme: Catalytic active RNA-molecules; act a enzyme
Plasmid: Small, mostly circular, autonomous replicated
DNA-molecules; extrachromosomale DNA, mostly present
in bacteria; are used in gene technology and biotechnology
to introduce foreign DNA into a organism
RNA-Interference: Natural mechanism of the genetic
regulation; inhibition of individual genes by specic RNAmolecules
neurogenesis: Formation of neurons (nerve cells)
mortality: Death rate
MRT (magnetic resonance tomography ): Medical
imaging method, displays structures of tissue and organs
of the body
Phase I (clinical trial): So called “First in Man“ (FIM);
clinical trial of drug in human regarding to tolerance
osteocyte: Cells that are present within the mineralized
bone matrix
p53: Intra cellular protein, regulates the cell cycle and
prevents the proliferation of cells including DNA damage
(tumor suppressor)
paracrine: Secretion modus of cells (e. g. release of
enzymes or hormones) affecting surrounding cells
s.c. (subcutaneous): Applied under the skin
polyclonal antibody: Anti bodies produced by different
B-lymphocytes, the physiological immune response is
always polyclonal
SCID: Severe Combined Immunodeciency
sheer-stress: Deformation of cells by a force
post mortem: After death
precipitation : Immunological reaction based on the
forming of an antigen-anti body complex that fallout from
a uid
SNP (single nucleotid polymorphism): Variation of single
base pairs within a DNA segment
Fraunhofer IZI-Leistungskatalog | IZI110-01