How can stem cells play a part?
Because MS is a complex disease, its successful treatment will likely require a combination of new treatments that control or heal each of the disease mechanisms: autoimmunity, loss of nervous system cells, and the inability of the central nervous system to regenerate the needed cells. Stem cells offer the promise of filling this therapeutic goal. They have an unparalleled regenerative capacity and the flexibility to grow into hundreds of different types of cells, including neurons and the cells that make the myelin sheath (called oligodendrocytes). Stem cells also modulate the immune system and can make factors that protect neurons.
Are there lots of groups working on developing a stem cell therapy?
There are numerous research teams around the globe working to develop stem cell therapies for MS. Their common goals are to identify which stem cells are best suited for the job, which signals will be able to coax them into becoming central nervous system cells, and the large scale lab methods required for ramping up the production of the needed cells.
Oligodendrocytes play a unique role in MS. These are the cells that wrap their myelin-filled membranes around nerve axons to form the myelin sheath. Nerve axons are the long skinny highways that transport electrical impulses from one nerve to another. The myelin sheath spirals around a nerve axon like layers of an onion. As the disease progresses, more and more layers are destroyed and only some regions of the nerve axon are repaired with new myelin. Eventually nerve axons are beyond fixing. Given the pivotal role played by oligodendrocytes, researchers are very keen to develop strategies to transplant oligodendrocytes grown from stem cells or stimulate resident brain oligodendrocytes in order to repair the damaged myelin sheath.
Stem cell research on MS is moving down a number of different avenues and some successes along the way have yielded early Phase 1 and 2 clinical trials. The majority of these are testing the safety of adult stem cells. Although scientists have long envisioned using stem cells as a source for replacing myelin-forming cells lost during MS, it is becoming increasingly clear that stem cells are also able to regulate the immune system. As we learn more about stem cells, researchers are hopeful that the knowledge gained can be translated into novel therapies for treating this disease.
Before basic stem cell research can be translated into the clinic for patients, it must first be rigorously tested and validated. For MS this involves transplanting stem cells into animal models to test if nerve conduction can be restored. Broadly speaking, ongoing MS research rests on two cornerstones. The first is preventing damage by modulating the immune system. The second is repairing damage by regenerating myelin and protecting nerve cells (neurons). The main types of stem cells being investigated are bone marrow stem cells (hematopoietic or mesenchymal), and brain stem cells (neural stem cells and oligodendrocyte precursor cells).
The road to finding a stem cell therapy for MS is paved with many challenges that will take time to overcome. But the wealth of information generated from labs around the globe is converging to help with the transition from basic research to the clinic. The results are promising and in time may point to a viable stem cell therapy for MS that can rid the body of harmful immune cells, repair the myelin sheath, and protect nerve cells.
A bone marrow stem cell transplantation therapy has shown strong success in stopping the progression of MS. Find out more here.
Current research using bone marrow stem cells
Scientists have found that the same therapy used for treating blood cancers called hematopoietic stem cell transplantation (HSCT) or, more commonly, bone marrow transplantation can be adapted to arrest the progression of MS. The theory is that newly transplanted stem cells won't carry the same memory that caused the autoimmune attack in the first place, and so they should be able to make new, healthy immune cells that won't attack myelin. Many Phase 1 and 2 clinical trials around the world have now tested whether autologous (from the patient) HSCT could be used to prevent progression of MS and the results are encouraging from all quarters. At present, the side effects from this therapy limit its use to only those patients with the most aggressive form of MS, but trials are also being considered for patients with less severe forms.
An important discovery is that mesenchymal stem cells are able to modulate the immune system cells that cause inflammation and attacks on myelin. Pre-clinical studies using mouse models of MS have also demonstrated that transplanting mesenchymal stem cells can protect neurons from further damage, improve functionality of the remaining neurons and even reduce scar formation, which is a key barrier to the repair process. The International Mesenchymal Stem Cell Transplantation Study Group supports the testing of intravenous autologous mesenchymal stem cell transplants as therapies to inhibit the autoimmune component of MS in patients for whom conventional agents are not working. The group has recommended further studies to test the biological activity of mesenchymal stem cells before using them to repair tissue.
Current research using brain stem cells
Because neural stem cells are able to differentiate into a variety of brain cells, they are considered an ideal source for replenishing depleted supplies of central nervous system cells. Early experiments looked very promising but more recent studies have shown that only very low levels of neural stem cells are making oligodendrocytes and neurons. All is not lost though, because other studies have shown that transplanted neural stem cells can stimulate the brain to make its own oligodendrocyte precursors. Transplanted neural stem cells also secrete factors that support neural cells and prevent inflammation and scar formation. Researchers think that these attributes are the ones that may alleviate symptoms in mouse models of MS. Pre-clinical studies have progressed to testing the ability of human neural stem cells in primates with an MS-like disease. The results are encouraging because the symptoms are lessened, perhaps through neural stem cells modulating the immune system.
Researchers are also devising strategies for stimulating oligodendrocyte precursor cells in the brains of patients with MS. These cells are distributed abundantly throughout the brain and, as the name implies, are able to make oligodendrocyte cells, which make the myelin sheath. Preliminary studies have shown that in the adult central nervous system these cells become activated when myelin is stripped from nerves. The precursors migrate to the damaged regions in the brain and, once there, become mature oligodendrocytes capable of making the myelin sheath. Understanding the pathways that lead to myelin formation and repair by oligodendrocyte precursor cells – and how these processes go awry – is a priority for the field and may lead to the development of novel drugs and reparative strategies.
Readers may wish to peruse the recommended sites and articles below for more information about MS and the possible applications of stem cells to treat this disease.
Research Summary of Stem Cells and MS (Stem Cell Network) (http://goo.gl/qq1bL)
MS Society of Canada (www.mssociety.ca)
National MS Society (www.nationalmssociety.org)
Multiple Sclerosis Resource Centre (www.ms-uk.org)
Multiple Sclerosis International Federation (www.msif.org)