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Human embryonic stem cells: an experimental and therapeutic resource?
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| MS in focus Issue
11
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2008
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Siddharthan Chandran, MRCP, PhD, Department of Clinical Neurosciences, Centre for Brain Repair, University of Cambridge, Cambridge, UK |
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The last decade has witnessed an unprecedented explosion of interest in stem cells in general and human embryonic stem (ES) cells in particular. It has excited at turns both hope and fear in a wide range of groups, from the familiar stakeholders through to policy makers and ethicists.
ES cells can generate a virtually unlimited supply of nerve cells (above) as an experimental and
drug discovery tool.
ES – the ultimate repair kit?
Most stem cells are restricted to making cells that belong to their tissue of origin. For example, nerve stem cells will make nerve cells.
Human embryonic stem cells (ES) can make all the cell types (over 200) that make up an individual. The twin property of being selfrenewing and pluripotent (unrestricted specialisation) means that ES may prove to be the ultimate body repair kit.
Where are they from?
ES are stem cells removed from embryos (four to five days old) obtained from fertility clinics.
These embryos were fertilised outside thebody (in vitro) and are donated for research under informed consent. The removed cells arethen grown on a layer of feeder cells in the presence of specialised medium-containing nutrients (cell culture). Over time the ES will proliferate and out-grow the starting dish and be reseeded onto several further dishes. The process will eventually result in the generation of many millions of ES, all from just a few starting ES.
 How can ES help scientists understand MS?
MS treatments have two aims: to prevent and to repair damage. Despite important advances in treatments (disease-modifying medications) that reduce relapse rate and some emerging evidence that early treatment may limit disability, no meaningful therapies are available to prevent or repair fixed disability.
Therapy development requires an improved understanding of the nature of disease evolution and the failure of recovery. Currently we use many animal-based systems to learn about MS. Although immensely valuable, there remains a great need to be able to study human cells. Until the advent of ES the possibility of widespread study of human cells was simply not possible.
An invaluable research resource for MS researchers would be access to unlimited numbers of human nerve cells and oligodendrocytes. ES make this feasible. In order to fulfil this possibility, scientists have first to understand the process or signals that direct an ES to become a nerve stem cell and then a nerve cell or oligodendrocyte. Much research focuses on this and borrows heavily on insights gained from studies of developing animals.
Once understood, these chemical signals can be applied under controlled conditions to drive ES to become nerve stem cells, neurons or oligodendrocyte cells exclusively.
If unlimited numbers of human nerve and oligodendrocyte cells were available, important questions could be addressed. For example, knowing more about the chemical signals between nerve cells and oligodendrocytes and how this language is disrupted in MS. Such knowledge may lead to therapies to restore the correct cellular dialogue in people with MS, thus promoting repair. The pharmaceutical industry is particularly interested in ES for this reason. An ample supply of human cells would provide a unique opportunity to test and discover new drugs.
Is there a role for cells made from ES to be used in MS?
It is incontrovertible that ES can generate a virtually unlimited supply of nerve cells as an experimental and drug discovery tool. It is less certain that ES have a role in cell-based therapies.
The damaged nervous system in people with MS can self-repair. Endogenous repair occurs when oligodendrocyte cells lay down new insulation around damaged nerves and thus effectively provide a protective “plaster” known as remyelination. Unfortunately in MS such repair is limited and inadequate. Stem cells could enable remyelination by either acting as a cellular reservoir of supportive factors that limit damage and/or enable endogenous remyelination. In addition, stem cell-derived cells, specifically oligodendrocytes, may be used to directly repair areas of injury. Animal models of MS support such an idea. However, given the fact that MS lesions can appear in diverse locations within the CNS, the method of administering such remyelinating cells has been a conceptual obstacle. Recent findings do provide some hope that intravenous delivery of nerve stem cells will allow distribution of cells to widespread areas of injury, an idea known as “homing”. However, there remain important issues to be overcome before stem cells can be considered for clinical trial. These include the development of clinically compatible ES and methods to ensure the exclusion of “contaminant” ES from “therapeutic” nerve stem cell preparations.
Conclusion
The science of ES is rapidly growing. The provision of unlimited numbers of human nerve cells for experimental study will accelerate our understanding and thus development of new therapies for MS.
Together this provides the basis for cautious optimism that meaningful therapies can emerge from ES.
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