Multiple sclerosis: how could stem cells help?

Over 400,000 people in the EU have multiple sclerosis (MS). It can cause blurred vision, extreme fatigue, pain, numbness, loss of movement and speech problems. It is the most common disease causing disability in young adults, and there is currently no cure. How could stem cell research help in the development of new treatments?

Multiple sclerosis (MS) is an autoimmune disease where a person’s immune system starts attacking and destroying myelin sheaths. When neurons lose their myelin, signals can’t be sent properly and the neurons begin to die. This leads to the symptoms of MS.

Stem cells in the brain naturally try to repair and replace myelin as damage occurs, but the immune system in MS patients will attack the myelin again.

There are currently no cell replacement treatments for MS, however research into using stem cells to ‘reset’ a patient’s immune system have shown promising results.

Researchers are interested in using stem cells to study MS and find ways to prevent and/or repair myelin damage.

Some studies are looking at using chemotherapy to destroy a person’s immune system and then use stem cells to build a new immune system that won’t attack myelin. This has had positive results in clinical trials and is now available as a treatment for relapsing-remitting MS patients who have not responded to the best disease-modifying treatments. Its use is restricted due to the dangerous side effects of this treatment.

Researchers are examining treatments and drugs that can harness and possibly enhance the ability of brain stem cells to naturally repair myelin.

Scientists are also trying to develop stem cell treatments to replace nerves destroyed by various neurological diseases, including MS.

Autoimmune diseases of all kinds are challenging to treat because the immune system attacks a patient’s own cells. Completely blocking the immune system is not possible as then the patient cannot fight infections.

Another challenge to developing MS treatments is that there is no single pattern to what causes the immune system of a person to start attacking the myelin sheath; the trigger causing the disease could be totally different in each patient.

Scientists still don’t fully understand how myelin sheaths are created by the nervous system. This makes trying to develop treatments to repair myelin sheaths very difficult.

Multiple sclerosis (MS) is a disease that affects nerve cells in the brain and spinal cord. In the healthy body, these nerve cells carry messages between the brain and the rest of the body, allowing us to move, balance, see, hear and feel. In MS, the body’s own immune system attacks the nerve cells so that they cannot function properly.

Nerve cell diagram
Healthy nerve cell: the cell is wrapped in a protective, insulating sheath called myelin.

Each nerve cell is wrapped in a protective sheath called myelin. If the myelin is damaged, the cell can no longer carry messages properly. This is what happens in MS. Depending on which nerves are damaged, patients may suffer from a range of symptoms, commonly involving problems with walking and sensation, bladder and bowel issues and fatigue. These symptoms appear for a time (known as a relapse) and then improve (remission), often going back to normal as the body repairs the damaged myelin. However, ultimately the nerve cells themselves are damaged and begin to degenerate, until eventually they stop working entirely. As the disease progresses, more nerve cells are affected, causing increasing disability (progressive MS).

There is currently no cure for multiple sclerosis but it is possible to treat the symptoms and reduce the number of relapses using medicine, exercise and physiotherapy. These treatments aim to help patients cope with symptoms or try to prevent damage to the nerve cells, but they do not help repair damage once it has occurred. Researchers hope that stem cell therapies may provide new approaches that can both prevent damage and enable us to repair it.

Stem cells are part of the body’s normal repair system – making new cells to replace those that get damaged or die. There are several different types of stem cells and scientists are investigating a number of ways they might be used to develop new treatments for multiple sclerosis:

  1. Preventing damage: It is possible to use certain types of stem cells to ‘reset’ the immune system (known as immunomodulation). The aim is to prevent the immune system from attacking the nerve cells, or reduce the amount of damage done.
  2. Repairing damage: Stem cells may be able to help repair the damaged myelin sheath, ‘remyelinating’ the nerves and allowing them to function correctly again. This could prevent the nerves themselves from degenerating. In the distant future, researchers hope that stem cells might be used to re-grow nerves that have been lost. However, this is much more complicated.
  3. Developing new medicines: stem cells can be used to grow nerve cells in the lab. These cells can be used to study how MS works, and to test potential new drugs.

The various approaches offer different advantages and may be useful for treating different types or stages of MS.

Blood stem cells

Blood stem cells are found in the bone marrow. They make the different types of cells found in the blood, including some cells that belong to the immune system and are involved in causing the damage in MS. MS patients have been given transplants of their own blood stem cells in an attempt to ‘reset’ the immune system. The patient’s existing immune cells are first killed using chemotherapy (treatment with powerful medicine). Blood stem cells previously taken from the patient’s own bone marrow are then injected into the blood stream with the aim of generating new immune cells that will not attack the body’s nerve cells. This method has shown benefits in relapsing-remitting MS patients, but not progressive MS patients. It is also a risky procedure, due to the suppression of the immune system making infections likely with a death rate of 1-2%. It is therefore only being used for patients with highly active forms of multiple sclerosis that do not respond to the best available drug therapies.


Mesenchymal stem cells

Mesenchymal stem cells (MSCs) are also present in the bone marrow. They normally form bone, cartilage and fat cells. Some researchers are investigating whether MSCs may help ‘re-train’ the immune system so that it does not attack the nerve cells, or may produce useful chemicals to help repair myelin. Studies in animals have shown some promising results and early clinical trials in patients are now taking place to see whether this may be helpful in humans.

Mouse neural stem cells
Mouse neural stem cells

The brain contains stem cells called neural stem cells. Addition of extra neural stem cells in rodents has recently been shown to have a similar action  to mesenchymal stem cells in producing useful chemicals to help brain repair. However, the brain’s own neural stem cells attempt to repair myelin after damage, but this process is inefficient and is not enough to repair all the damage caused by MS over time. Researchers hope to find ways to encourage these neural stem cells already present in brains to do a better repair job, or to add new cells to improve repair. Improving repair of the myelin sheath would enable the nerve cells to send messages again and would reduce degeneration of the nerves.

Current research is focused on understanding how neural stem cells carry out repair, and on searching for drugs that will enhance the repair process using the cells already in the patient’s brain. In the longer term, it may be possible to transplant new neural stem cells, nerve cells or myelin-forming cells into the brain, but this would be a much more complex process and the new cells would first have to be grown in dishes in the laboratory, for example from embryonic stem cells or induced pluripotent stem cells.

Embryonic stem cells and induced pluripotent stem cells can produce every type of cell found in the body. Researchers have developed ways to control these stem cells to make human nerve cells and myelin in the laboratory. These lab-grown nerve cells do not yet meet the strict safety and purity standards that would be needed for transplantation into patients, but they do give researchers a valuable opportunity to study the problems that occur in MS. They can also be used to test the effects of potential new drugs. Carrying out studies on cells may help to speed up the progress of drug development because important information can be obtained in the early stages of a study using cells, before research on animals is required.

Some MS patients with relapsing-remitting MS, and aggressive disease which does not respond to our best drugs, can now be treated with chemotherapy and replacement of blood stem cells. However, this is currently restricted due to large risks that outweigh the benefits for most patients. Several other types of stem cells are being investigated for their potential use in future treatments for more MS patients: stem cells may be able to repair the myelin on nerve cells or perhaps in the long-term may even be used to grow completely new nerve cells. Stem cells are unlikely to cure multiple sclerosis but in the future may be able to slow, stop or even reverse the progress of the disease. However, much more research is needed to establish whether the different sorts of stem cells can provide safe and effective treatments for MS, and how those cells should be used.

This factsheet was created by Claire Keith

Reviewed in 2012 by Anna Williams and Gianvito Martino.

Reviewed and updated in 2015 and 2018 by Anna Williams.

Lead image of mouse neural stem cells by Gianvito Martino. Other cell images by Anna Williams.