Download Stem cell science - Hope not hype

Stem Cell Science: Hope not Hype
The Biotechnology and Biological Sciences Research Council (BBSRC) and the Medical Research
Council (MRC) are the principal public funders of biological and medical research in the UK. They
are part of the Research Council UK (RCUK) partnership, which includes five other research
councils. These pages feature research funded by BBSRC and the MRC.
BBSRC April 2011
With special thanks to:
Dr Martin Baron, The University of Manchester
Dr Kelly BéruBé, Cardiff School of Biosciences
Professor Jeremy Brockes, University College London
Dr Iphigenie Charatsi, UK Stem Cell Bank
Dr Nicholas Daudet, University College London
Francisco Figueiredo, Newcastle University
Dr Alex Gould, MRC National Institute for Medical Research
Julian Hitchcock, Field Fisher Waterhouse LLP
Professor Anthony Hollander, University of Bristol
Dr Richard Oreffo, University of Southampton
Dr Sari Pennings, The University of Edinburgh
Professor Paolo Salomoni, University College London
Professor Lorraine Young, The University of Nottingham
What’s so special about stem cells?
From ethical concerns to miracle cures, stem cells have been widely debated over
recent years, but what are they really and what can we realistically expect from
research into them?
We have hundreds of different types of cells in our bodies with functions ranging from
transporting oxygen to helping us remember where we put our keys. These cell types are
specialised to carry out very specific functions, but they all came from just one single cell the fertilised egg.
Stem cells are the key to the way this single cell becomes a whole complex organism and over decades scientists have been gradually teasing out their secrets.
Stem cells are special because they aren’t specialised to have a particular function.
Instead, they can give rise to a number of different cell types – for some types of stem
cell, this could be absolutely any type of cell at all.
As well as building us in the first place, stem cells are important in repairing and renewing
our bodies throughout our lives. Their capacity to renew is tremendously exciting
because if it could be harnessed, it may be possible to use it to cure diseases including
Alzheimer’s disease and some types of cancer.
But we aren’t there yet…
Tried and tested: Bone marrow transplants
Every year thousands of patients with leukaemia, lymphoma
and some other cancers are treated with stem cells taken
from their own, or a donor’s, bone marrow. Blood stem cells
from bone marrow can turn into any sort of blood cell and
can replace the cells destroyed during cancer therapy.
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Where do stem cells come from?
Two types of stem cell occur naturally - embryonic stem cells and adult stem cells
• Embryonic stem (ES) cells come from embryos about five days after fertilisation,
when the embryo is a ball of 50-100 cells. ES cells can give rise to any cell type in
the body (they are pluripotent) and this potential makes them especially interesting.
Human ES cells come from leftover embryos donated by couples following IVF
treatment. In the UK, ES cells can only be created under licence and cell lines
produced must be deposited in the UK Stem Cell Bank.
• Adult stem cells are partly specialised. They are not as versatile as embryonic
stem cells and can produce only a limited number of cell types. For example, the
stem cells in bone marrow produce many types of cell, including blood cells and
cells that make bone and cartilage, but not nerve cells. There is probably a type
of adult stem cell for most types of cell in the body and more types are still being
discovered.
Scientists can now produce stem cells in the lab which, like embryonic stem
cells, can produce any type of cell. There are two types of these induced pluripotent (IPS) stem cells and somatic cell nuclear transfer (SCNT) stem cells
• IPS cells are made by reprogramming adult cells so that they behave like
embryonic stem cells. This is done by re-introducing four embryonic genes that
have been switched off in the adult cell. This type of stem cell has great potential
both as a tool for understanding diseases and in stem cell therapy.
• SCNT stem cells are made by transferring the cell nucleus (which contains the
cell’s DNA) from an adult cell into an unfertilised egg cell that has had its own
nucleus removed. This cell then divides, forming an embryo from which the stem
cells can be harvested.
Human admixed embryos are made in the same way, but combine an adult human
cell and an animal egg cell. This technique was developed because of a shortage of
donor human eggs. Like all human embryos produced for research, human admixed
embryos are very carefully regulated. They can only be grown for up to 14 days and
it is illegal to implant them into humans or animals.
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Regenerative medicine - getting the most from your
personalised repair kit
There is huge potential for treatments using stem cells. If their capacity to renew and
regenerate tissue really can be harnessed, we may be able to build and repair parts of
the body without the possibility of rejection.
This could lead to breakthroughs in the treatment of many degenerative and ageingrelated diseases. Treatments for diseases such as insulin-dependent diabetes, Parkinson’s
disease and Alzheimer’s disease are probably 10-20 years away but for other diseases and
conditions, carefully controlled trials are already taking place.
In 2009 the MRC funded four early stage clinical trial projects using adult stem cells for bone
repair and for treatment of leukaemia, Addison’s disease and blindness. These projects aim
to transplant or stimulate patients’ own stem cells.
Restoring sight
The eye’s cornea is maintained by limbal stem cells (LSCs). When these cells are lost
or don’t behave correctly, the cornea breaks down, causing severe pain and blindness
– a condition known as Limbal Stem Cell Deficiency (LSCD). A few LSCD patients have
been treated successfully using laboratory-grown LSCs, but the animal products used
to grow the cells increase risk of disease transmission. Now, scientists at Newcastle
University are running a larger trial using cells grown without animal products. They are
also developing methods for storing LSC cells – an important step towards making LSC
treatment widely available.
A transplant breakthrough
In 2008 a patient received a replacement windpipe made with the help of her own stem
cells.
The transplanted organ was made using the windpipe of a donor that was treated to
remove all the donor’s cells and then repopulated with cartilage cells grown by scientists
at the University of Bristol from the patient’s own bone marrow stem cells. The transplant
was a great success and, since the windpipe contains only the patient’s own cells, the
risk of rejection is very low. Similar procedures have since been carried out in two more
patients.
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Stem cell promise – could we really grow new limbs
in the lab?
Getting stem cells to behave the way we want them to and make cells of the
right type to be used in medicine is a big challenge and not without risk.
There’s still a long way to go, and much of the promise from stem cells lies well in the
future, but stem cell researchers are slowly gathering the clues that could help turn
the possibility into reality.
An arm and a leg
Salamanders can re-grow lost body parts and understanding how this happens could
provide important insights for regenerative medicine. Researchers at University College
London have discovered that a protein called nAG boosts multiplication of the stem
cells needed for re-growth of the newt’s missing limb. By artificially triggering cells to
produce the protein, the scientists were able to induce limb regeneration even after the
nerve, where the protein is naturally produced, had been removed. Learning more about
the molecular signalling needed to start limb re-growth, may eventually open up the
possibility of mimicking the effect in humans.
Learning from birds about hearing loss
In the inner ear are sensory hair cells essential for hearing. Their loss through trauma
or ageing can result in deafness. In birds and cold-blooded vertebrates, these hair
cells can regenerate from stem cells in the ear, but this doesn’t happen in humans.
Researchers at University College London are studying the inner ear of the chicken to
understand the mechanisms that control hair cell regeneration. In the long term, they
hope their research will lead to new cures for human deafness.
Stem cells and brain development
A team at the MRC National Institute for Medical Research in London has identified
genes in the fruit fly Drosophila that control how large the developing brain becomes.
Within the growing brain, stem cells divide to produce more and more neurons until an
upper limit is reached. The scientists found that two ‘timer’ genes tell stem cells when to
stop dividing and prevent the brain from growing too large. Uncovering the mechanisms
that regulate cell proliferation will improve understanding of what happens during
cancer, when cells multiply inappropriately.
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Studying stem cells - more than medicines
Stem cells offer exciting possibilities for medical treatments themselves,
but studying them can teach us many other things too.
Epigenetics in disease
Epigenetic changes are modifications to DNA that alter the way the cell interprets the
genetic code. All cells essentially have the same DNA, but different genes are active in
different types of cell; epigenetic changes control which genes are active in each cell.
Sperm and egg cells are specialised for different things, so they have different epigenetic
changes. When an egg cell is fertilised, the epigenetic changes are reset to create
embryonic stem cells. Researchers at the University of Edinburgh are investigating this
resetting process in mouse egg cells. By working out how epigenetic changes are reset
they hope to understand processes involved in certain cancers and in some types of
serious brain disorders associated with these changes.
Stem cells and cancer
Scientists at the MRC Toxicology Unit have found that the tumour suppressor protein Pml,
which is known to have an effect on blood cells, is also important in controlling the growth
of neural stem cells in the developing brain. This could have important implications for
containing brain and nervous system cancers as Pml might be able to halt tumour growth.
For the first time, scientists at University College London have discovered that cancers
of the lung, mouth, oesophagus and cervix contain a group of stem cell-like cells. This
means the cells are capable of growing to form a new tumour – a possible reason why
these cancers may be difficult to treat. The researchers think future chemotherapy
strategies for patients with cancer may be more successful if this population of stem cells
is identified and targeted alongside standard treatment.
Reducing the need for animal testing
Researchers at the University of Cardiff are using stem cells to develop micro-lungs
that could replace rats in testing the toxicity of new chemicals. To make the lung cells
behave more like a real 3D lung, they are coating them onto the outside of polymer
micro-spheres.
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Stem cell therapy’s big challenges
Regenerative medicine using stem cells is advancing fast, but there are some
major hurdles to overcome before stem cell treatments can become commonplace.
• How can we be sure treatments are safe?
• How can we build cells into 3D structures to build whole organs?
• How can we make stem cells specialise into the right type of cell?
How can we be sure treatments are safe?
• Stem cells’ amazing potential comes from their ability to divide and repair, but how can we
be sure that this won’t go out of control? Is there a risk of stem cells given for treatment
becoming tumours?
• If the cells used don’t come from their recipient, how do you overcome the problems of
rejection?
How can we make stem cells safe for transplantation?
Researchers in Edinburgh are paving the way for safe transplants of stem cells made
from skin cells. Scientists had found ways of reverting adult cells to stem cells by using
retroviruses to reintroduce genes that are switched off when the cell specialises. However,
because retroviruses can cause cancer, this method could never be used for treatments.
The Edinburgh team, working with colleagues in Canada, found a virus-free way to
introduce the genes, reprogramme the cell and then remove the genes leaving no trace.
Stem cells made through this technique offer new ways of understanding diseases and
testing new drugs.
How can we reliably make enough of the right sort of cells to use for
treatments?
Any stem cell treatment needs high quantities of cells, so for stem cell treatments to
become part of mainstream medicine, we will need to develop ways of producing and
storing large numbers of stem cells.
At the universities of Nottingham and Loughborough, a team of stem cell biologists
and biomanufacturing engineers are using their expertise to investigate the problems
of growing stem cells on an industrial scale. They hope to find a way of automating
and optimising production of human embryonic stem cells.
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Regenerative medicine’s big challenges
How can we build cells into 3D structures to construct whole organs?
Scientists can now grow 2D sheets of cells of different types fairly successfully,
but growing 3D tissues is a much bigger challenge.
Growing bones
Researchers at the University of Southampton are developing computer models that
predict the biological processes needed to make bone tissue.
They are doing this using a combination of data from laboratory experiments on bone
stem cells and mathematical modelling.
Eventually, the researchers hope to apply what they have learned to help them develop
simple laboratory methods for growing bone for use in patients.
How can we make stem cells specialise into the right type of cell?
If stem cell therapies are really going to reach their full potential, we need to
understand as much as possible about the mechanisms that determine their
specialisation.
Learning what controls cell development
Notch is an important gene involved in many aspects of cell development and
differentiation from the formation of nerve cells to bone healing. It is also involved in some
cancers. Researchers at the University of Manchester are using fruit flies to study Notch
and learn more about how its structure relates to its function. A better understanding of
how Notch works could be applied to help make the right types of cell for specific stem
cell therapies.
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Regulations
UK regulations on stem cell research are some of the most comprehensive in the world.
All embryonic stem cell research in the UK is regulated under the Human Fertilisation and
Embryology Act (2008). Only fertility research and research into serious diseases is permitted
under the Act, and embryos can only be kept up to 14 days of development. The embryos
used must have been donated with appropriate consents.
Donation of unwanted embryos following IVF treatment is done purely altruistically; the donor
has no further rights over the cells and will not benefit financially from any treatment that is
developed. Human embryonic stem cell lines created in the UK can only be produced under
licence and have to be deposited in the UK Stem Cell Bank.
Stem cell lines can also be made from embryos created by SCNT and from human admixed
embryos. These embryos must be destroyed before they reach 14 days of development. It
is illegal to use artificial sperm or eggs, or any embryo containing non-human material for
reproduction but it is permitted to produce them for approved research.
Who owns stem cells?
Each stem cell line is unique and has different properties. For example, it may tend to give rise
to a particular type of cell, or carry the genes for a specific disease. These unique properties
– which can take a lot of time and effort to work out – can potentially make the cell lines quite
valuable, so it is often in researchers’ interests to take out patents to protect their intellectual
property. Intellectual property and patenting in this area is very complex and differs depending
on the type and origin of the cell line.
Banking on success
In 2003 BBSRC and the MRC set up the UK Stem Cell Bank (UKSCB) – the first of its kind in the
world – to provide researchers with ethically sourced, well characterised cell lines, tested and
cultured to international quality control standards.
All embryonic stem cell lines developed in the UK must be deposited in the UKSCB. By 2010,
80 stem cell lines originating from the UK and elsewhere, had been approved for deposit in the
Bank, including lines suitable for clinical use.
This centralised resource provides an accessible source of standardised, quality controlled stem
cells for approved research worldwide. Individual scientists don’t need to create their own lines
meaning that fewer embryos need to be used for research.
Cord Blood Banking
Pregnant women in some areas of Britain can choose to put their baby’s cord blood – taken from
the umbilical cord and placenta – into the NHS Cord Blood Bank. Cord blood is a rich source of
stem cells and cord blood stem cells seem to be more versatile than other types of adult stem
cell – scientists are still investigating their true potential. The banked blood is stored for use in
transplants in a similar way to bone marrow. Commercial cord blood banking is also available.
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Finding out more
UK Stem Cell Initiative
The research councils are members of the UK Stem Cell Initiative, created by the
Government in 2005. Other members include the Department of Health, the UK Stem Cell
Foundation, the Academy of Medical Sciences, medical research charities and industry.
Stem Cell Dialogue
In 2008, BBSRC and MRC commissioned a public dialogue* on stem cells. Issues were
discussed with representatives from the general public, research science, industrial
science, social science and religious and faith groups. These pages have been produced in
response to dialogue recommendations.
* Funded by Sciencewise-ERC
Links to other organisations
Research Councils UK - www.rcuk.ac.uk
Biotechnology and Biological Sciences Research Council - www.bbsrc.ac.uk
Medical Research Council - www.mrc.ac.uk
Engineering and Physical Science Research Council - www.epsrc.ac.uk
Economic and Social Research Council - www.esrc.ac.uk
UK Stem Cell Bank.
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