A question on stem cells answered by Dr Jack Antel.
Is there any stem cell research taking place in multiple sclerosis?
“Stem cells” can be broadly defined as cells which retain the potential to develop into mature cell types. These can be classified into two major categories:
Ø cells that retain the capacity to develop into any cell type (“pleuripotential stem cells”)
Ø cells that can only develop into nervous system cells (“neural progenitor cells”).
The rationale for research into the role of “stem cells” in the process of remyelination in multiple sclerosis (MS) includes:
· examination of MS tissues and magnetic resonance based studies of MS patients indicate that some remyelination does occur.
· Studies in rodents demonstrate that the extensive remyelination that can follow demyelination induced by viruses, toxins, or immune mediated mechanisms is mediated by “stem cells” rather than by oligodendrocytes that produced the initial myelin and were then damaged.
· Analyses of adult human brain tissues indicate that “neural progenitor cells” exist in the normal adult brain and around MS lesions.
Current “stem cell” research focuses either on inducing such cells present in the nervous system (endogenous cells) to become myelinating cells or providing new sources of such cells (exogenous cells). As regards endogenous cells, challenges faced include providing necessary signals that will induce “stem ‘cells” to become myelin forming cells. Studies of development of oligodendrocytes in immature animals and of “stem cells” maintained in tissue culture are helping identify factors (molecules) that are critical to direct the process. An active question is whether “stem cells” in the mature nervous system, will respond to such signals. Remyelination in MS may also be limited by molecules that inhibit entry of “stem cells” into lesions and their subsequent differentiation into myelinating cells.
As regards provision of exogenous “stem cells”, challenges being faced include what is to be the source of such cells. The prototype pleuripotential cell capable of becoming any cell type is the embryonic stem cell derived from the newly fertilized ovum. “Stem cells” found in the blood or bone marrow can readily be expanded into large numbers and used clinically to re-constitute populate the immune system. Some of these cells can migrate to the nervous system following transfusion into the blood but have only a limited if any capacity to become nervous system cells. Experimental studies in animals show that neural progenitor cells isolated from the nervous system, can successfully mediate myelination when transplanted into the nervous system of animals who lack myelin due to genetic defects or whose myelin has been damaged by disease. When such cells are administered into the blood, some access the nervous system but relatively few become actively myelinating cells. They may however provide molecules or signals that support the function of progenitor cells already resident in the nervous system. Whether “neural progenitor cells” can be isolated and expanded from non nervous system sources (eg skin) remains under study; if derived from the individual for whom they would be used, the problem of immune rejection faced if another individual provides the cells, would be by-passed.