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STEM CELL AND
ITS POTENCIES IN THE FUTURE
All images in this document is removed due to copyright restriction
Ahmad Aulia Jusuf
Bagian Histologi
Fakultas Kedokteran Universitas Indonesia
2009
TRANSPLANTATION OF UMBILICAL CORD BLOOD STEM
CELL INTO PATIENT WITH MAJOR THALASEMIA
Straits Times, 28th Jun 2002
 Boy treated for Thalassemia Major in Singapore in 2001

Monday, May 22,
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Stem Cells?
Monday, May 22,
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AGENDA






Introduction
Definition
Characteristic and types of stem cell
Resource of stem cell
Potency and application of stem cell in medicine
Controversy in bioethical of using stem cell
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INTRODUCTION

In the last decade the
interests and researches
about stem cell has been
establishing well




therapy of the untreated
diseases conservatively
or surgically
getting the new drugs
study the pathogenesis of
the diseases
Potency in business
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DEFINITION

Stem cell

unspecialized cells

differentiate into many various
types of specific cells


to generate the various tissues
in the body sel
self regenerate / self renew

the ability of stem cells to divide
and produce more stem cells
Monday, May 22,
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Mouse Embryonic Stem Cells
Monday, May 22,
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Human Embryonic Stem cells
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CHARACTERISTICS AND TYPES OF STEM CELL

Characteristics

ability to differentiate

the potential to develop into
other cell types





nerve cells
cardiac cells
skeletal muscle cells
pancreatic cells etc
self regenerate / self renew

the ability to divide and
produce more stem cells
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CHARACTERISTICS AND TYPES OF STEM CELL

Types of stem cell

Totipotent

differentiate into embryonic and
extra embryonic cell types


placenta and umbilical cord
zigote dan morula



ultimate embryonic stem cell
differentiate into many various
cell
each cell in morula can develop
to become one complete
organism
 has capacity to make the
placenta and umbilical
cord
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CHARACTERISTICS AND TYPES OF STEM CELL

Types of stem cell

Pluripotent
 differentiate into cells
derived from any of the
three germ layers



ectoderm, mesoderm and
endoderm
not the placenta and
umbilical cord.
embryonic stem (ES) cells

the cells obtained from
the inner cell mass of
blastocyst.
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CHARACTERISTICS AND TYPES OF STEM CELL

Types of stem cell

Multipotent
 differentiate into a closely
related family of cells


hematopoietic stem cells
 differentiate into red
blood cells, white
blood cells, platelets,
etc
Neural stem cells
 differentiate into
nerve cells (neuron)
and glial cells
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CHARACTERISTICS AND TYPES OF STEM CELL

Types of stem cell

Unipotent

differentiate into only one cell type but still have the property of self renewal

Erythroid progenitor cell can only differentiate into erythrocytes
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RESOURCE OF STEM CELLS

Zigot


the ultimate stem cell
produced from the fusion of
an egg and sperm cell
Embryonic stem cells

the cells obtained from the
inner cell mass of blast cyst



an early stage embryo
approximately four to five
days old in humans
consisting of 50–150 cells
obtained commonly from the
of unused embryos in the
IVF (in vitro fertilization)
procedure
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RESOURCE OF STEM CELLS

Embryonic stem cells


still controversy due to
the ethical issues
in the media of culture
broth

differentiate into




heart muscle cell
skin cell nerve cell
hepatocyte
etc
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RESOURCE OF STEM CELLS

Fetus


usually obtained from
abortion clinic
Umbilical cord blood


obtained from the blood
of umbilical cord and
placenta just after birth
2 types of stem cells



hematopoietic stem cells
mesenchymal stem cells.
another types of stem
cells

Monday, May 22,
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neuron like stem cells
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RESOURCE OF STEM CELLS

Umbilical cord blood

Characteristics



low immunogenecity
no needs the invasive
procedures
no needs 100% matched
of HLA (human leucocyte
antigen)
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RESOURCE OF STEM CELLS

Adult Stem Cells
 any cell found in a
developed organism

has 2 properties


the ability to divide
and create another
cell like itself
divide and create a
cell more
differentiated than
itself
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RESOURCE OF STEM CELLS

Adult Stem Cells

obtained from

Bone marrow



hematopoeitic stem
cells
stromal or
mesenchymal stem
cells
Other adult tissues





central nervous tissue
adipose tissue
skeletal muscle
pancreas
etc
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RESOURCE OF STEM CELLS

Adult Stem Cells

plasticity or transdifferentiation

ability to differentiate into multiple cell types



hematopoietic stem cells

three major types of brain cells (neurons, oligodendrocytes, and astrocytes)

skeletal muscle cells

cardiac muscle cells

liver cells
Bone marrow stromal cells

cardiac muscle cells

skeletal muscle cells
Brain stem cells

blood cells

skeletal muscle cells
Monday, May 22,
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Plasticity of Adult Stem Cell
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Various types of stem cells
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APPLICATION OF STEM CELL

Gene therapy


the hematopoetic stem cells can
be used to carry the transgene
into the patient body
a possibility of administration
transgene containing stem cells
into the body only in one times


the stem cells has the property
of self renewing
hematopoietic stem cells can
differentiate into many various
blood cells

transgene may present in many
cell types
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APPLICATION OF STEM CELL

Studies of biological
processes



developmental process of
organism and cancer
facilitated by the ability to
trace stem cell fate
Research to discover and
to develop the new drugs

investigate the effect of
drugs on the tissues
Monday, May 22,
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APPLICATION OF STEM CELL

Cell based therapy


Stem cells can be cultured
and manipulated in the
laboratory
followed by transplantation
them into the patient in
treatment of the diseases
without disturbing the
function of the body
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THE APPLICATION OF STEM CELLS IN THE THERAPY OF
THE DISEASES
 Cell based regenerative therapy
 The

to do the transplantation of stem cells in the target organ
 The


principle
aims
to achieve the development and the growing of new healthy
cells in the tissue or organ of the patient
to replace the impaired specific cells due to the diseases or
trauma with the new transplant cells
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THE APPLICATION OF STEM CELLS IN THE THERAPY OF
THE DISEASES

Cell based regenerative therapy

The advantage of using stem cell in cell-based therapies







Potential to be harvested from patients so it can avoid the possibility of
rejection reaction in the recipient
High capacity of cell proliferation in culture to obtain large number of cells from
a limited source
Ease of manipulation to replace existing non functional genes via gene
transfer methods
Ability to migrate to host's target tissues, e.g. the brain
Ability to integrate into host tissue and interact with surrounding tissue
It does not need the matching of tissue properties between donor and
recipient
Autologous transplantation is better to be used.
Monday, May 22,
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THE APPLICATION OF STEM CELLS IN THE THERAPY
OF THE DISEASES
 Cell based regenerative therapy

To avoid the rejection of the stem cell in the recipient

the Somatic Cell Nuclear Transfer (SCNT) or therapeutic cloning method

the method in transferring the stem cells to the recipient without rejection
reaction
 the patient's DNA is injected into an enucleated unfertilized egg and
used to generate ES cells
 The ES cells then are cultured and transplant into the patient
 The stem cells in the desired organ or tissue then differentiate into the
specific cells such as beta cell of pancreas, heart muscle etc.
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THERAPEUTIC CLONING/ SOMATIC CELL
NUCLEAR TRANSFER (SCNT)
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THERAPEUTIC CLONING/ SOMATIC CELL
NUCLEAR TRANSFER (SCNT)
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THE APPLICATION OF STEM CELLS IN THE THERAPY
OF THE DISEASES

Embryonic stem cells


In the past it was thought that embryonic stem (ES) cell may
proliferate in the unlimited number
Nowadays it has already known


the proliferation of stem cells is limited due to the mutation in their genes,
stimulated by the nutrient broth in culture media
The advantages of using of ES cells in Cell based therapy in the
therapy of diseases




Ease to be obtained from the fertilization clinic
It is pluripotent stem cell
It is immortal cell that can proliferate in hundred times.
Low rejection reaction
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THE APPLICATION OF STEM CELLS IN THE THERAPY
OF THE DISEASES

Embryonic stem cells

The disadvantages of using ES cells in the therapy of diseases




It has the possibility to become cancer (tumorigenic)
It is allogenic transplants that has an implication in the rejection reaction due to
immunological process
It is still a controversy in the ethical issues
Adult stem cells

The advantages of using adult stem cells in the therapy of diseases




It can be isolated from the tissue of patient itself
The limited capacity to differentiate into another cells
It does not have the controversy in ethical aspect
The disadvantages of using adult stem cells in the therapy of diseases



the number of stem cell is very small in the mature tissue
the limited of lifespan
it is a multipotent stem cells
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EMBRYONIC STEM CELLS
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THE APPLICATION OF STEM CELLS IN THE
THERAPY OF THE DISEASES

Umbilical cord blood stem cell


It is believed to be a new hope in the cell based therapy
The advantages of using cord blood stem in the therapy of diseases






It is ease to be obtained from the umbilical cord blood bank
It is ready to use because it has been screened, tested and freeze.
It has minimal viral contamination than bone marrow stem cells
The procedure is very simple
The risk of Graft Versus Host Disease (GVHD) is lower than bone marrow
stem cells
The disadvantages of using cord blood stem


the risk of genetic diseases
it is impossible to obtain sufficient numbers of stem cells from most cord
blood collections to engraft an adult of average weight
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THE APPLICATION OF STEM CELLS IN THE THERAPY
OF THE DISEASES
The potential diseases that can be treated using the
stem cells
Parkinson and Alzheimer
 Spinal cord injury
 Stroke
 burns
 Heart diseases
 Diabetes

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osteoarthritis
 Cirrosis hepatis
 Leukemia
 Anemia sel sabit (sickle
cell anemia)
 Cancer

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APPLICATION OF STEM CELLS IN THE THERAPY
OF CEREBRO VASCULAR DISEASE

In the past there is a dogma from Cajal, a famous
scientist in neurology


the impairment of nerve cells in the brain was permanent and the
nerve cells had no capacity to regenerate
Nowadays this dogma has been change


the nerve cells in the brain have plasticity
the stem cells has been discovered in the brain
Monday, May 22,
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APPLICATION OF STEM CELLS IN THE THERAPY
OF CEREBRO VASCULAR DISEASE

Research of using cord blood stem cells in the therapy of
cerebrovascular disease give the good result

In Mouse



the cord blood stem was injected into the mouse in which its media
cerebri artery had been occlusion
The function of the brain increased to 70% in the group that received the
cord blood stem cells
In Human

Intravenous injection of mesenchymal stem cells MSC isolated from bone
marrow into the brain of 30 patient with cerebrovascular diseases
increased the function of the brain according to the Barthel Index and
modified Rankin Scale
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The Barthel index before (day 7) and after (3, 6, and 12
months) cell therapy
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The modified Rankin score before (day 7) and after
(3, 6, and 12 months) cell therapy
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APPLICATION OF STEM CELLS IN THE THERAPY
OF INFARCT MYOCARD DISEASE

In the acute myocard infarct

the circulating bone marrow stem cells and stem cells in
the heart moved to the damage area




the number is not enough
make the heart muscle and perform the neovascularization
The additional exogenous stem cells
Bartinek had done the intracoronary infusion of
bone marrow stem cells (autolog)


on the 22 patients with acute myocard infarct
got the good result
Monday, May 22,
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APPLICATION OF STEM CELLS IN THE THERAPY
OF INFARCT MYOCARD DISEASE
 There is the evidence
 Embryonic
and adult stem cells can replace the
damage heart muscle and gives neovascularization
Strauer inserts the mononuclear bone marrow (autolog) into
the occlusion artery when doing the percutaneus
transcoronary angioplasty 6 days after myocard infarct
 patient received the stem cells




has the smaller infarct area
smaller index of stroke volume
Increasing the left ventricular end systolic volume, the contractility of heart muscle in
the infarct area and mocard perfusion
Monday, May 22,
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Stem Cell on the Myocard Infarct
Monday, May 22,
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APPLICATION OF STEM CELLS IN THE SKIN
REPLACEMENT
 Stem Cells Pada Skin Replacement
 Keratinocytes
isolated from hair follicles can make
epidermis

permits the epidermal transplantation from its own patient
and avoids the rejection reaction
 The
usage of skin replacement is useful in the
therapy of wide skin wound and traumatic burn
Monday, May 22,
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BIOETHICAL ISSUES IN USING OF STEM CELLS
 Using of stem cells especially embryonic stem
(ES) cell in the research and treatment of the
human diseases may implicate in the arising of
ethical problems
 Several ethical issues



Is the use of embryo in the research that implicates in the death of
embryo itself violates the human right?
Is the use of excessive embryos from the IVF procedures for the
research permitted ethically?
Is the research to make human embryos in which their body parts are
used for treatment of human diseases ethically permitted?
Monday, May 22,
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BIOETHICAL ISSUES IN USING OF STEM CELLS

The main issue is the resource of stem cell itself

Embryonic stem (ES) cells are obtained commonly from several resource


Cloning of human embryos in order to get the stem cells is the
controversial issue



abortion, the excessive embryo from IVF procedure and cloning process
It has correlation with the issue of “the beginning of life” and the respect of life
itself
Cloning of human embryo is prohibited by all of the religions
The procedures in harvesting the stem cells from human embryos
will destroy the embryo and make the embryo to be death


There is the argument that the status of human embryo is same with the
human itself.
All of the procedures in collecting the stem cells from human embryo are not
permitted by the religion
Monday, May 22,
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BIOETHICAL ISSUES IN USING OF STEM CELLS

The status of human embryo is still debatable

Does the human embryo has to be appreciated as the human




it has a potency to be the human
it is a part of human life
Furthermore Is it true that the developing human embryo is an organism?
Using of embryos obtained from the excessive human embryo in
the IVF procedure are still controversy

There is a moderate argument


it is better to use those embryos in research and therapy of human diseases
rather throw them away
But it is also an other argument

those embryos have to keep alive until they die naturally
Monday, May 22,
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There is a fundamental question:
Does the stem cell has a potency
to become a cancer in the future?
Monday, May 22,
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Future Experiments????
ButterCat
Monday, May 22,
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CatCow
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Future Experiments
Catrilla
Monday, May 22,
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Future Experiments
SparrowBoxer
Monday, May 22,
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TigerOwl
51
We Need More Basic Research on Stem Cells
?
Monday, May 22,
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Monday, May 22,
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Monday, May 22,
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