Stem cells are part of the body’s normal repair system which replaces damaged or dying cells where possible. Stem cells are unspecialised as they haven’t developed to carry out a particular function yet. Each stem cell has the potential to develop into one of a number of different cell types depending on the body’s needs at a particular time, such as becoming a nerve cell, a red blood cell or a heart muscle cell. Once they’ve undergone this change they’re known as specialised cells and they can’t go on to change again.
Researchers are exploring whether it’s possible for stem cells to become cell types which could slow MS disease activity, repair existing damage or replace faulty parts of the immune system or nervous system. Although stem cell therapy is routinely used for conditions such as cancer of the blood (leukaemia), it’s still largely seen as an experimental treatment for multiple sclerosis (MS).
The most studied type of stem cell therapy for MS is autologous haematopoietic stem cell transplantation (often shortened to AHSCT, ASCT or HSCT). This uses your own stem cells, which are collected and then injected back into your body. Early results have been encouraging and understanding how best to treat people with stem cells is improving.
AHSCT has not been formally assessed for use in the NHS outside clinical trials, but a small number of centres have begun to provide it on the NHS under specific circumstances to a very small number of people. People accepted for treatment generally either have a very aggressive type of MS or continue to have relapses even after trying one or more disease modifying drugs.
How is AHSCT thought to work in MS?
Haematopoietic (pronounced hee-mato-poy-etic) stem cells are found mainly in our bone marrow, although small numbers circulate in our blood. They develop into the different types of cells found in the blood including some cells which are part of the immune system. They’re produced in large numbers throughout our lives to continually replenish our blood and immune system as cells die and are replaced.
The aim of AHSCT is to replace or reboot your body’s immune system so that it no longer attacks your myelin or causes inflammation in your brain and spinal cord. AHSCT uses high doses of chemotherapy to wipe out your existing immune system, which is then rebuilt using stem cells collected from your blood before you have the chemotherapy. The hope is that your rebooted immune system will stop attacking you and there will be no further damage.
Using your own stem cells minimises the risk of them being rejected by your body. If the stem cells come from someone else (a donor) it’s known as an allogeneic transplant – this is associated with a higher risk of complications than an autologous (self) transplant, so it’s not generally used for MS.
What does the AHSCT procedure actually involve?
There are six main stages to the procedure, the first five take place over several weeks.
The first stage is known as mobilisation, where a combination of drugs are given to encourage your blood cells to move from your bone marrow and into your blood stream so they can be collected. Mobilisation is carried out by giving an infusion (through a drip) of a chemotherapy drug (cyclophosphamide) and injections of a synthetic form of a natural growth factor called G-CSF (granulocyte-colony stimulating factor). Your MS symptoms can get temporarily worse during this phase.
Stage two involves collecting (or harvesting) your stem cells, it typically happens about 10 days after mobilisation once blood tests have shown that there are enough stem cells present in your bloodstream and takes between half a day and one day. You are connected to a machine which collects your blood through a needle in your arm, separates out the stem cells and then returns all the other components of the blood to your body.
The third stage involves freezing (or cryopreserving) your harvested stem cells, ready for when they are returned to your body at a later stage.
Stage four of the process is another round of chemotherapy, known as conditioning chemotherapy, this gets your body ready for the return of your stem cells. It may involve either completely wiping out (myeloablative or high intensity chemotherapy) or partially eliminating (non-myeloablative or low intensity chemotherapy) your bone marrow and immune system, hopefully destroying the cells that are involved in MS disease activity. More recent procedures have tended to use the less aggressive lower intensity chemotherapy method. This stage usually takes several days and you may need to take drugs to control any nausea and vomiting which are common side effects of the chemotherapy. You may also be given steroids to dampen down any immune reactions.
The fifth stage is transplantation, also known as stem cell return, where your stored stem cells are thawed and returned to your blood by infusion (through a drip). This is often a couple of days after the conditioning chemotherapy and will only be done once all the chemotherapy drugs have cleared from your system. It takes a couple of hours and is similar to having a blood transfusion. The stem cells make their way to your bone marrow (engraftment) and should start making new blood and immune cells within 10 to 30 days. During that 10 to 30 day period, you have, in effect, no immune system which explains some of the risks and side effects set out below.
The final stage
The sixth and final stage is recovery. AHSCT is a complex, aggressive procedure and recovery can take a considerable length of time. You should expect to be off work for quite a while as typically you need three to six months to recuperate from the procedure. However, some people can take more than a year to recover.
Risks and side effects of AHSCT
There are several potential side effects both during and after the procedure.
Susceptibility to infection, also known as being immunocompromised, is common immediately after the conditioning chemotherapy and until your immune system has been rebuilt by your stem cells following the transplantation stage. You should be closely monitored by your health professionals to make sure that you remain as well as possible and you are likely to be in an isolation room in hospital for several weeks. Both you and any visitors will need to take precautions to avoid introducing infections. What might normally be a low threat to your health can be very serious, even life threatening, during this period. Also, previous infections, particularly with the viruses that cause shingles, cold sores and herpes, may become active again. You may be given antibiotics and transfusions to support you through this vulnerable time.
It’s possible to develop other autoimmune conditions, particularly autoimmune thyroiditis where the body sees the thyroid, and the hormones it produces, as threats and so attacks them.
You may experience side effects from the chemotherapy, which can include fatigue, weakness and a temporary loss of appetite. You will be at an increased risk of bleeding and bruising and your MS symptoms may also be worse for some time. Hair loss is common but should only last between one and six months, although your hair may grow back a slightly different colour or texture. Other longer term side effects can include lowered fertility, or early menopause, if high dose chemotherapy has been used.
There is a risk of dying due to the procedure. Although treatment procedures are improving, clinical trials since 2001 have still had treatment-related death rates of one or two people in every 100 (1.3%), according to analysis by the European Group for Blood and Marrow Transplantation (EBMT). The majority of deaths were due to infections. However, looking at transplants carried out since 2005, the mortality rate has decreased further still to around 1 in 330 (0.3%).
Is AHSCT available for MS in the UK?
Until recently, treatment with stem cells was seen as purely experimental for people with MS and was only available in the UK through clinical trials. However, treatment is becoming available through the NHS at a very small number of centres, but the number of people who are accepted for treatment is extremely small.
In the UK, any hospital performing transplants, including stem cell therapy, must be accredited by the Joint Accreditation Committee - ISCT & EBMT (JACIE). The transplant centre has to show that procedures are being carried out to agreed standards by suitably trained staff. Accredited centres are inspected regularly to make sure that these standards have been maintained.
The centres that we are aware of offering treatment on the NHS are in Sheffield and the London MS-AHSCT collaborative group. People are usually only accepted if they have a very aggressive form of MS, or if they continue to have relapses even after trying one or more of the disease modifying drugs. Each hospital will have its own specific eligibility criteria but they may follow the guidelines developed by the European Group for Blood and Bone Marrow Transplantation.
Based on the data from clinical trials, you’re more likely to respond to treatment, and therefore be suitable for AHSCT, if you meet the following general criteria:
- you have relapsing MS or progressive MS with evidence of continuing inflammatory disease, for example, active lesions are seen on recent MRI scans
- you are continuing to have relapses when on a disease modifying drug treatment (at least one drug tried – though some centres suggest that AHSCT should only be considered in people who have relapses even after treatment with Lemtrada (alemtuzumab) and/or Tysabri (natalizumab), or in whom these drugs cannot be considered)
- you are early in your MS disease course before the onset of any significant irreversible disability. Disability is often measured using the EDSS scale. Exact requirements will vary but would typically require the ability to walk at least 100m with or without using a single walking aid and with or without resting (EDSS of 6 or below)
- you are fit enough to undergo the treatment regimen.
In addition, people with very aggressive MS, who have developed severe disability in the previous year, may be accepted for AHSCT.
The MS Trust is working in conjunction with the London group to conduct the first ever audit of a real-world UK MS stem cell service run outside of a clinical trial. From this audit we hope to understand how people with MS can be assessed and selected for stem cell treatment on the NHS, and what is needed to develop safe, high quality services for the future. We will report on the results of the audit as soon as they become available.
We are only aware of one clinical trial which is recruiting participants in the UK at the moment:
- MIST (Multiple sclerosis International Stem cell Trial or Stem Cell Therapy for Patients with Multiple Sclerosis Failing Alternative Approved Therapy; NCT00273364), is recruiting in Sheffield. It is part of a multicentre trial administered by Northwestern University in Chicago. Only a small number of people, around one or two per month, are being recruited in the UK. If you are interested in joining this trial, you should check the inclusion and exclusion criteria using the link above. If you are eligible, you would need a referral from your usual neurologist or GP to Professor Basil Sharrack, the neurologist, and Professor John Snowden, the haematologist, at Sheffield who are running the trial.
More clinical trials may take place in the UK in the future. You can check for any new trials on the Clinical Trials website using the search term “multiple sclerosis AND stem cells” and then using the map function to focus in to the UK.
A small number of centres are also beginning to offer stem cell treatment privately in the UK. According to the Sheffield website, they have limited capacity for overseas patients and fee paying patients from outside England. To discuss this option you would need to contact their dedicated private patient team.
Harley Street at University College Hospital have begun to offer AHSCT for MS and are following the EBMT guidelines.
London Bridge Hospital are also considering patients on a case by case basis. Approval for suitability appears to be through the London MS-AHSCT Collaborative Group with referral then made to the private group.
If you are considering AHSCT, whether through the NHS, a trial or privately, you would need to be referred by your usual neurologist or GP to the relevant haematologist and neurologist. Both specialists would need to assess your suitability for treatment.
Treatment outside the UK
There are clinics around the world that are offering stem cell treatment for MS on a commercial basis. This is sometimes known as stem cell tourism. Some, but not all of the centres, are offering AHSCT. There are other forms of stem cell treatment being researched in MS, which you can read more about later, but these are not as far advanced as AHSCT, so if you are considering going abroad you need to check exactly what kind of treatment is being offered.
The standards set by JACIE (mentioned above) have been adopted in some other countries. You can see a list of JACIE accredited centres in the UK and abroad. Other countries may have their own standards, for example FACT in the USA.
We are aware that centres in Mexico, Russia and Israel are offering the AHSCT procedure to people with MS, including people with progressive MS. The cost of treatment varies widely but can range between £30,000 and £85,000. If you are considering going abroad, it will be important to find out:
- exactly what kind of treatment is provided – is it AHSCT or something else?
- whether the clinic is regulated to international standards
- whether others have benefited from treatment at the clinic
- what follow up is provided
- how safety, side effects and the effectiveness of treatment are monitored over time
- what is, and is not, included in the price quoted and what you will need to pay for in addition to flights and possibly hotel accommodation, for example whether there will be any additional medications that you have to pay for once you’re home. The risk of having additional costs may be high if you develop complications after the initial treatment.
It will also be essential to make sure that there will be proper follow up and support in place once you have returned to the UK.
When considering any treatment, it is vital to weigh up all the different factors, discuss your options with health professionals, family and friends before deciding what seems best for you as an individual. It is important to look critically at the risks and not only the hope that is offered.
Below is our list of suggested actions if you, or someone you care about, think that AHSCT may be an appropriate treatment option:
Get independent information - If you would like to know more about stem cell therapies, it is important to seek accurate, unbiased information from trusted sources. The MS charities and independent stem cell organisations, such as EuroStemCell, the International Society for Stem Cell Research and the European Society for Blood and Marrow Transplantation, are a good place to start for a balanced overview. You can access some of their factsheets and other information using the links in the section below called Find out more.
Seek the opinion of your MS specialist team - consult your MS team as they know you and your MS well. If your relapses are not well controlled by a disease modifying drug, they may suggest that you try an alternative. In some circumstances, your MS team may agree that AHSCT is appropriate. You will need a referral from your neurologist to take part in some clinical trials or to attend most hospitals providing AHSCT. You may need to provide some evidence of your MS disease activity, such as a recent MRI scan, or your history of previous treatments.
Your MS team will remain involved with your longer term care once you have recovered from the AHSCT procedure and no longer need the involvement of the AHSCT multidisciplinary team.
Check the credentials of the team - check that the hospital where you will be treated has experience of stem cell transplantation in people with MS as worldwide experience is limited to a few centres. Visit the websites of clinics offering treatment to understand exactly what they offer and to whom, the process you would need to go through, the cost and any follow up support that is available. You could ask the clinics for any information sheets and eligibility criteria. Treatment should include assessment by an MS specialist neurologist and a haematologist working together as part of an AHSCT multidisciplinary team. Treatment should be explained in a written “informed consent document” in a way that you can easily understand. You should have the opportunity to ask questions at all stages of the process.
Clinic websites will probably include personal stories but may only show you their most successful cases. You may be able to get a more accurate idea of success rates by asking on forums or groups, such as Facebook, although, inevitably, people are more likely to talk about successes than side effects, complications or failure. Some people with MS have blogged about their experiences of having stem cell therapy.
Balance the risks and benefits to your health - stem cell therapy has the potential to bring significant benefits to some people with MS. Good progress is being made through clinical trials and the outcomes of treatment are improving as more is learned. However, as research is still at an early stage, stem cell therapy is not widely practised and the results of treatment for a particular person cannot be predicted. The risks should be very carefully considered, including the possibility of treatment-related death, and weighed up against the potential benefits.
Find out about after care - it is important to know what care will be available after your AHSCT treatment especially if you are considering going abroad. What support will be available if you experience complications or side effects? This should be outlined exactly so that you know what to expect and who to contact if you have any concerns.
Consider the costs - treatment in a clinical trial should be free. In addition, a very small number of people are being accepted in the UK for treatment on the NHS. The quotes for treatment abroad vary widely. Before making any commitment, it is important to establish the full costs of treatment including assessment, tests, treatment and follow up appointments. You will need to budget for your travel and for hotel costs for anyone going with you. You may also need accommodation for yourself if you are discharged from hospital but don’t feel strong enough to travel home straight away, or if you develop complications and need to extend your stay.
It is important to be cautious as there have been examples in the past of unscrupulous people making a profit by offering worthless treatments to people with MS at very high costs. Some clinics did not even check whether a person had MS or not.
Other stem cell research strategies being explored for MS
Some research teams are looking at using other types of stem cells and different strategies to AHSCT for MS. However, this research is at a much earlier stage than AHSCT and the potential benefits in MS are less well understood.
The second form of cell therapy being tested in MS also uses cells from the bone marrow, but the focus is quite different – the aim is to try and protect nervous tissue from damage and encourage the repair of existing damage. The type of stem cells most commonly being tested for this approach are mesenchymal (pronounced mez-en-kai-mal) stem cells which are found in the bone marrow, some other adult tissues and also in the placenta and umbilical cord blood of new born babies. Mesenchymal stem cells usually develop into bone, cartilage and fat cells, they have repair properties but cannot generate nerve cells or oligodendrocytes themselves. Another type of cells that can be used for this approach are mixed mononuclear cells, this is a mixture of all the different bone marrow stem cells which are used together. These forms of cell therapy do not aim to replace the person’s own immune system, and so do not require pre-treatment with cancer chemotherapy drugs, so they are less aggressive than AHSCT.
An example of this approach is the ACTiMuS trial which is taking place in Bristol. This two year study will involve 80 people with primary or secondary progressive MS. Mesenchymal stem cells will be collected from participants' bone marrow. In the first year, one group will have their stem cells reintroduced by infusion into a vein whilst the placebo group will receive a blood transfusion. In the second year, the groups will be reversed.
The study will look for changes in nerve conduction inside the brain and spinal cord. It will also use a range of other measures to study alterations in disease progression, in particular, extensive and innovative MRI techniques. The study builds on a previous small safety trial in Bristol that suggested this approach to treatment with stem cells might have an effect on progression. The researchers are not looking for more participants. The trial is expected to finish in October 2018.
Some overseas clinics are offering mesenchymal stem cell transplants. If you are considering this type of treatment, bear in mind that its benefits in MS are less well known.
The third strategy is to replace damaged oligodendrocytes or restore their ability to make myelin. This treatment is being investigated using a type of stem cell known as induced pluripotent stem cells (iPSCs). Induced pluripotent stem cells do not occur naturally in the body, they are cells that have already become specialised, which are harvested and then reprogrammed in the laboratory to behave like stem cells. iPSCs can then be manipulated to turn into oligodendrocytes. However, this form of stem cell therapy for MS is at a very early experimental stage, though early clinical trials to test its safety are currently being planned, particularly in the USA.
It is this ability of stem cells to regrow damaged or missing brain and spinal tissue that often captures people’s attention and imagination when it comes to stem cell therapies in MS, but it is currently the furthest off in terms of becoming a clinical treatment.
As MS seems to have two disease processes, inflammation – leading to relapses, and neurodegeneration – resulting in progression, different types of stem cell therapy may be needed to reduce inflammation than to encourage repair.
Future directions for stem cell research in MS
The UK research community is very active in this area and includes groups in Bristol, Cambridge, Edinburgh, Nottingham, Sheffield and several teams in London. Most centres undertake research in the laboratory and with people with MS in the clinic.
Stem cell treatments have huge potential for the future treatment of people with MS but the disease process in MS is still poorly understood so more information is needed. Key questions for research include:
- How can stem cells be encouraged to develop into cell types that can treat MS?
- Which cells or systems in the body should be targeted?
- Why do some people benefit more than others from treatment?
The results of these avenues of research should allow the design of more effective clinical trials and produce better outcomes for people with MS.
- JAMA 2015;313(3):275-284. Full article Association of nonmyeloablative hematopoietic stem cell transplantation with neurological disability in patients with relapsing-remitting multiple sclerosis.
- American Journal of Stem Cells 2013;2(2):95-107. Full article The development of hematopoietic and mesenchymal stem cell transplantation as an effective treatment for multiple sclerosis.
- Current Neurology and Neuroscience Reports 2014;14(9):478. Summary Autologous bone marrow transplantation for the treatment of multiple sclerosis.
- Neurology 2017;88(9):842-852. Full article High-dose immunosuppressive therapy and autologous HCT for relapsing-remitting MS.
- JAMA Neurology 2017;74(4):459-469. Summary Long-term outcomes after autologous hematopoietic stem cell transplantation for multiple sclerosis.
- Bone Marrow Transplant 2012;47(6):770-790. Full article Haematopoietic SCT in severe autoimmune diseases: updated guidelines of the European Group for Blood and Marrow Transplantation.
- Nature Reviews Neurology 2017;13(7):391-405. Summary Autologous haematopoietic stem cell transplantation for treatment of multiple sclerosis.
- CNS Drugs 2017;31(6):453-469. Summary Cell therapy for multiple sclerosis.
- Multiple Sclerosis Journal 2017; Apr 1:1352458517703802. [Epub ahead of print] Summary Pilot trial of intravenous autologous culture-expanded mesenchymal stem cell transplantation in multiple sclerosis.
Last updated: November 2017
Last reviewed: November 2017
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