Is stem cell therapy the answer for patients with MS? A question playing on the minds of every person effected by the debilitating disease, whether diagnosed or not. With new research into the part that stem cells can play in resetting the immune systems of patients with MS, different procedures and treatments are being trialled around the world to find a way to stop or improve the symptoms of this incurable disease. I chose to study stem cells in MS because my mother was diagnosed with the disease when she was 20. I wanted to learn more about the disease, and what researchers are finding in their ongoing search for a cure.
Multiple Sclerosis is condition that attacks the nerves in the brain, spinal cord and optic nerves. An environmental trigger causes the immune system to produce inflammation and attack the central nervous system, and this slows or stops nerve conduction. This is because myelin, the protective film around the axon of the nerve, is stopped from being produced by oligodendrocytes. The damaged areas of the nerve fiber, called lesions, cannot be healed unless the oligodendrocytes can produce more myelin at the damaged site, meaning that most of the damage caused by MS is progressive and in some cases, irreversible.
The most common form of MS, relapsing-remitting MS, attacks in clear periods of time (relapse) where the motor skills or other neurological factors worsen in the patient. A relapse is then followed by remissions, which gives the patient a period of partial or complete recovery, where the factors may completely disappear. This form may eventually lead to secondary progressive MS, where patients will experience a gradual decline in their symptoms. Primary progressive MS effects the patient’s neurological function, and this will decline steadily. Some may experience occasional plateaus or periods of minor improvement, even though there are no clear remission and relapse periods. Progressive-relapsing MS is the rarest form of the disease, where it steadily progresses from the beginning, with no remission periods and occasional periods of strong effect.
There is no clear cause of MS. Some factors that are linked to a patient being diagnosed with MS include the migration patterns and location of the patient, a possible triggering virus, genetic factors such as a first degree relative with the disease already, a lack of certain vitamins and nutritional factors, and new research shows that there may be a link with a mutation in the NR1H3 gene. But, all of these factors do not have enough evidence to support them as a confirmed cause of MS.
The current treatment for MS is dependent on how the disease is effecting the patient. There are two general categories for MS treatment; medication to mitigate the symptoms, or to modulate the immune system. Immunotherapy medications slow down the frequency and severity of attacks. This means that the myelin layer will not develop such severe lesions, and the damage will be less severe. Methlprednisolone is a steroid medication to also control the severity of an attack, but this drug stabilises and lessens the inflammation at the affected site. Immune suppressants such as methotrexate or mitozantrone are sometimes used in patients with progressive MS. None of these treatments provide any repair or complete halt of an attack nor can they prevent or stop attacks from occurring.
Stem cells would provide different sorts of treatments and benefits to patients with MS, compared to the drugs that are available today. There are numerous approaches that researchers are looking at for stem cell use.
The first approach is to use chemotherapy to wipe out the patient’s existing immune system, and then use their own stem cells from their bone marrow to replenish the blood system. This method has been branded the autologous haematopoietic stem cell transplant (AHSCT), and uses chemotherapy to aggressively wipe out the immune system. This treatment is currently available through two clinical trials at St. Vincent’s hospital in Sydney, and the Austin hospital in Melbourne. This treatment is not suitable for all types of MS, and patients are only recommended by their doctor if there are no other therapies working, or they cannot be used on the patient. This treatment may be able stabilise or improve the disability of people with MS, but it comes with great risks for the patient and is not guaranteed to give the patients improvement in the disease. The outcome of this method, ideally, is that the newly regenerated immune system will not attack the myelin around the nerves, or other brain tissue.
The second approach is to use the patient’s mesenchymel stem cells, which are the cells that are isolated from the connective tissue of other organs and tissue (stroma). The cells can come from various places in the body, but an experiment conducted by Steven A. Goldman (MD PhD, University of Rochester) successfully transplanted stem cells derived from human skin into the brains of mice, and those cells developed into myelin-making cells, that then formed new myelin quickly and efficiently for the nerves. Another research team in Italy, led by Gianvito Martino (MD) have forced mouse skin stem cells to become myelin-making cells, and put them in the spinal cord of mice with an MS-like disease (called experimental autoimmune encephalomyelitis – EAE). This prompted some recovery in the mice, but the cells never actually produced myelin. Instead, they appeared to release growth chemicals which stimulated the natural repair processes of the mice, and reduce inflammation. With these results, we can assume that similar things would happen in humans, but there would need to be further research conducted. The outcome of this method, depending on which method is used, would be to lower the immune system’s response to the nerve cells, enhance the growth of myelin, or reduce inflammation and trigger the natural repair process of the nervous system and the brain tissue.
The third approach is to use stem cells to grow and replace oligodendrocytes that are lost in MS. Dr Mirella Dottori, Dr Junhua Xiao and Prof Trevor Kilpatrick (University of Melbourne) all investigated how they could use laboratory-grown oligodendrocytes, from stem cells, in the brain, for them to produce myelin in the nerves. The use of the patient’s own cells would prevent rejection from the immune system, and the cells (labelled ‘iPS’ cells) have a similar potency to hESCs. These iPS cells are from reprogrammed specialised adult cells, in the lab, and are capable of generating any other types of tissue. Dr Dottori and her team have developed a reliable method of creating immature oligodendrocytes from these cells. The outcome is to then let these cells produce myelin in the brain.
The fourth and final approach is to use placental stem cells to reduce the disease. A research team led by Prof Claude Bernard and Dr Natalie Payne, conducted at Monash University’s Australian Regenerative Medicine Institute, looked at the potential, of a variety of stem cells, for their ability to modify the immune response in MS and assist with repair. Human amnion epithelial cells (hAECs) were specifically looked at. These cells are obtained from human placentas, which are usually discarded after birth. In a single placenta, there are a large number of cells available for use, and these cells have the same potency of hESCs and are unlikely to be rejected by the patient after infusion. In a number of detailed experiments, the team has shown that hAECs are able to suppress the amount of activity of T immune cells, and reduce the number of inflammation-producing chemicals from the cells. When these cells are infused into mice with EAE, they were able to stop the further development of the disease. This response in mice was associated with a reduction in inflammatory T cells and an increase in the number of ‘calming’ T regulatory cells. The outcome of this method is to calm the response of the immune system, and ultimately stop the disease from progressing.
In terms of an ethical, social, legal and economical perspective on stem cell therapy for MS, there are minimal concerns. Unlike most stem cell treatments which require human embryonic stem cells (hESCs), taken from the blastocyst of an embryo, these treatments mainly use cells that are taken from the patient. The placental stem cells raise minimal ethical concerns, as the placenta is usually disposed of after the child is born. Socially, the use of placental stem cells may raise some concern because of the new trends in parents keeping the placentas for their own nutritional purposes. But, this should not be so much of a problem that they could not be used. Economically, the research projects still being conducted by scientists need funding. In Australian research projects, most teams have received incubator grants, and funding from MS Australia, a leading contributor in MS research.
To conclude, the use of stem cells in the treatment of MS looks promising. With the number of research projects being conducted, and the number of methods being trialled, a treatment with stem cells which stops or improves the effects of MS will definitely be available in the future. People affected, like my mum, may have a definite answer faster than they think.