Stem cells - factsheet
Date of issue: July 2012
This factsheet will be reviewed within three years
Stem cells offer great promise for treating MS and possibly repairing some of the damage caused to the central nervous system.
This factsheet provides an overview of areas being explored by researchers and some of the studies that have taken place.
1. What are stem cells?
Stem cells are naturally occurring cells that differ from other cells in the body in that:
- they are able to divide and renew themselves for long periods of time - known as proliferation
- they are unspecialised - meaning they are not modified to have a specific function in the body
- under specific conditions they have the potential to develop into cells with special functions - known as differentiation. For example, stem cells have the potential to differentiate into beating muscle cells of the heart, cells that produce insulin in the pancreas or nerve cells in the brain.
There are two main types of stem cells - embryonic stem cells and adult stem cells.
Embryonic stem cells
Embryonic stem cells are found in the developing embryo. These cells are capable of developing into all cell types that make up the tissues and organs of the human body.
Adult stem cells
Adult stem cells are found in some adult tissues and organs, including bone marrow, blood and the brain. The role of adult stem cells is to help the body repair itself by replacing cells that are lost through general 'wear and tear', injury or disease.
Adult stem cells are more limited in the types of cells they can differentiate into - typically into the type of cell in the tissue where they are found. Some examples are:
- Haematopoietic stem cells - found in bone marrow, blood and also the umbilical cord of newborn babies. Can differentiate into all of the different types of blood cells including red and white blood cells and platelets.
- Mesenchymal stem cells - found in bone marrow, skin, fat tissue and other sites. Can differentiate into tissues including bone, cartilage and fat cells.
- Neural stem cells - found in the brain. Neural stem cells can differentiate into the major cell types in the brain, including neurons (nerve cells) and oligodendrocytes (myelin-forming cells).
2. Potential uses of stem cells
Embryonic stem cells
Research on human embryonic stem cells only began in 1998 when it was discovered how to isolate cells from an embryo and grow them in a laboratory. Embryonic stem cells are usually collected during the blastocyte stage (about five days after fertilisation) when the embryo only contains 50-150 cells. These cells are said to be pluripotent, as they can differentiate into any type of cell found in an embryo or adult. By studying embryonic stem cells in the laboratory, scientists will identify the factors that control when a stem cell differentiates as well as the type of specialised cell it develops into. This will then give an insight into how stem cells may be used therapeutically.
Adult stem cells
Research on adult stem cells started in the 1960s and haematopoietic stem cells from bone marrow have been used to treat blood disorders, such as leukaemia, for around thirty years. Over the years, adult stem cells have been found in more tissues than scientists originally expected.
Originally, adult stem cells were thought to be multipotent; meaning they are only able to differentiate into a few different cell types. However, evidence suggests that some (but not all) adult stem cells might be induced to become pluripotent1. This ability of some adult stem cells to develop into more cell types than expected is called plasticity. Examples of adult stem cell plasticity include:
- brain stem cells that can differentiate into blood cells
- mesenchymal cells from bone marrow that can become heart muscle cells
- haematopoietic stem cells that can develop into liver cells.
Research includes trying to find ways of growing adult stem cells in the laboratory and understanding how to control the signals that enable adult stem cells to differentiate into the required cell type. If adult stem cells do prove to have greater plasticity than was originally thought, they could be more useful for stem cell therapies than expected and avoid the ethical issues associated with cells derived from embryos.
Stem cell research and MS
Most stem cell treatments have involved encouraging cells to grow into large numbers of cells in the laboratory and then transplanting them into the recipient. Although this technique is termed a 'transplant', the cells are returned to the body as an infusion into a vein.
Three possible theories as to how stem cell treatment might work in MS have been explored:
- stem cells develop into nerve cells to repair damage to the brain
- stem cells develop into oligodendrocytes to repair damage to myelin
- stem cells boost the immune system to reduce or prevent damage occurring.
Taking a different approach, groups in Cambridge and Edinburgh have investigated the potential for encouraging stem cells already present in the central nervous system to develop into oligodendrocytes capable of repairing myelin without the need to first extract them2. Initial work in rats has identified potential targets for drug treatments but further work is needed to test whether this mechanism will work in people with MS.
The consensus is that any treatment based on stem cells is still some years away. To be useful for transplant purposes there are many questions that still require answering and there is a need for research that shows:
- sufficient numbers of stem cells can be grown
- cells can successfully be controlled to develop into the type of cell required
- transplanted cells survive, integrate and function in the recipient
- transplanted cells do not harm the recipient.
3. Possible risks of stem cells
The potential benefit of stem cells is balanced by risks that still have to be assessed and overcome. Much more work is needed to ensure stem cells can be controlled and are safe to use.
Possible risks include:
- Unwanted cell development: there is a risk of uncontrolled cell development and the possible growth of tumours.
- Immune rejection: the source of the stem cells can have implications for the body's acceptance or rejection of the transplant.
- autologous transplants - recipients receive their own stem cells
In an autologous transplant the cells will not be rejected by the immune system because the person is receiving their own cells.
- allogeneic transplants - recipients receive stem cells from a donor
In an allogeneic transplant there is a risk of immune rejection and cells have to be matched as closely as possible to the recipient to avoid this.
Transplantation of embryonic stem cells would be an allogeneic transplant and therefore there is a possibility that the recipient could reject the cells. Whether this would actually happen has not been determined yet in human experiments.
- Suppression of the immune system prior to transplantation: a number of trials have required using drugs to suppress an individual's immune system before the stem cell transplant. This can leave the recipient more prone to infection and the drugs used can be very toxic to the body.
4. Clinical trials
Although work with stem cells is still at a very early stage, there have been small clinical trials in people with MS in both Europe and the United States. These trials investigated the benefits of transplanting haematopoietic stem cells harvested from the bone marrow or the blood of the participant, ie an autologous transplant of adult stem cells. These trials were classed as phase I/II trials as they involved small numbers of people.
Below are some of the published results of clinical trials on stem cell treatments for MS:
European Group for Blood and Marrow Transplantation (EBMT)
In 2006, the EBMT reported on a retrospective survey of 178 people with MS who had received haematopoietic stem cell transplants following suppression of the immune system3. This showed that stem cells produced a slowing down of disease progression in participants affected by severe, progressive multiple sclerosis.
In 2011, the same group reported mixed results on the long-term effects of stem cell therapy in people followed for between two and 15 years4. Treatment appeared to be most beneficial to younger people (35 years or less), those recently diagnosed, and those with highly inflammatory MS.
People with progressive MS responded less well. Overall, 16 of the 35 participants showed a small improvement in EDSS scale scores (a measure of disability) and this improvement lasted for an average of two years. For two people the improvements lasted for over seven years. Seven people who had initially shown improvements worsened during the follow-up period, but remained better than their original disability level at the start of treatment. Disability scores for seven participants worsened and two people died due to the effects of the treatment.
Division of Immunotherapy, Northwestern University
A study in Chicago5 involved 21 people with relapsing remitting MS who had had two relapses in the previous year, despite treatment with beta interferon. The injection of autologous stem cells followed courses of treatment with immune suppressing drugs.
Participants were followed for an average of three years. All 21 showed no worsening of disability as measured by the EDSS scale, and 17 improved by at least one point. 16 people experienced no further relapses following stem cell treatment.
The researchers reported that this treatment is 'a feasible procedure that not only seems to prevent neurological progression, but also appears to reverse neurological disability'. A second, larger, multicentre trial with study centres in North and South America6 is underway, with results expected in 2013.
Institute of Clinical Neurosciences, Frenchay Hospital, Bristol
In a phase I study7, researchers assessed the safety and feasibility of treating six people with stem cells derived from their own bone marrow. Participants did not receive treatment to suppress their immune system before their stem cells were infused.
Participants were followed up for a year and no serious adverse effects were found. Clinical measures indicated that their MS was stable. The Bristol team were encouraged by the results, which will be investigated further in a phase II/III clinical trial with a longer follow-up period.
University of Cambridge
Researchers in Cambridge studied the feasibility and safety of treatment with autologous mesenchymal stem cells from bone marrow in ten people with secondary progressive MS who had visual problems8. No serious adverse events occurred and improvements were seen in some aspects of vision. The research suggests that this treatment may have a neuroprotective role, protecting nerves from MS related damage, although this will need to be studied further in larger trials.
5. Stem cell tourism
Stem cell treatments are being offered commercially on the internet, though these sites should be approached with great caution. In some instances, clinics have been found to be offering expensive treatments with no evidence that they work or are safe and providing little in the way of follow-up support for customers. In perhaps the most high profile example, Dr Robert Trossel, who provided stem cell therapies at clinics in the Netherlands and Belgium, was found guilty of exploiting vulnerable people with unsupported claims about treatments, which, in some instances, were found to contain cells derived from cows. He was struck off the UK Medical Register in 20109.
The same year, a panel of British doctors and scientists warned of the risk to health and finances of visiting private stem cell clinics around the world - so called 'stem cell tourism'10.
The International Society for Stem Cell Research (ISSCR) has published a patient handbook11 to help people evaluate stem cell therapies they may be considering.
The MS Trust is not currently aware of any ethical, authorised clinics using stem cells to treat MS outside clinical trials.
- Takahashi K, Yamanaka S.
Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors.
- Huang JK, Jarjour AA, Nait Oumesmar B, et al.
Retinoid X receptor gamma signaling accelerates CNS remyelination.
Nature Neuroscience 2011;14:45-53.
- Saccardi R, et al.
Autologous stem cell transplantation for progressive multiple sclerosis: update of the European Group for Blood and Marrow Transplantation autoimmune diseases working party database.
Multiple Sclerosis 2006;12(6):814-823.
- Fassas A, et al.
Long-term results of stem cell transplantation for MS: a single-center experience.
- Burt RK, Loh Y, Cohen B, et al.
Autologous non-myeloablative haemopoietic stem cell transplantation in relapsing-remitting multiple sclerosis: a phase I/II study.
Lancet Neurology 2009;8(3):244-253.
- Hematopoietic stem cell therapy for patients with inflammatory multiple sclerosis failing interferon: a randomized study.
Current Controlled Trials website
- Rice CM, et al.
Safety and feasibility of autologous bone marrow cellular therapy in relapsing-progressive multiple sclerosis.
Clinical Pharmacology and Therapeutics 2010;87(6):679-685.
- Connick P, et al.
Autologous mesenchymal stem cells for the treatment of secondary progressive multiple sclerosis: an open-label phase 2a proof-of-concept study.
Lancet Neurology 2012;11(2):150-156.
- Stem cell doctor Robert Trossel struck off.
Daily Telegraph, 29 September 2010
- Pownall M.
Experts warn against "tourist trap" stem cell therapies.
- International Society for Stem Cell Research (ISSCR).
Patient Handbook on Stem Cell Therapies. Issue Date: December 2008. [cited 2012: June 14]
Available from URL: http://isscr.org/clinical_trans/pdfs/ISSCRPatientHandbook.pdf
Please contact the MS Trust Information Team if you would like any further information about reference sources used in the production of this publication.
7. Glossary of terms
Adult stem cell - an undifferentiated cell found within an adult tissue that has the potential to differentiate into a specialised cell type of the tissue it is found within
Allogeneic transplant - recipients receive cells/tissues that are taken from a different individual of the same species
Autologous transplant - the donor and recipient of the cells/tissue are the same person
Differentiation - the process by which a stem cell develops into a specialised cell
Embryonic stem cell - an undifferentiated cell found within an embryo that has the potential to differentiate into a wide variety of specialised cell types
Haematopoietic - an agent that promotes the formation of blood cells
Mesenchymal stem cells - adult stem cells found in bone marrow, skin and fat tissue and other sites
Multipotent - able to develop into more than one type of differentiated cell
Neuron - nerve cell
Oligodendrocyte - myelin forming cell
Plasticity - the ability of stem cells from one adult tissue to develop into the specialised cell type of another tissue
Pluripotent - able to develop into any type of cell found in the embryo or adult of that species
Proliferation - the expansion of a population of cells by the continual division of individual cells to produce two identical cells