Cellular approaches for stimulating CNS remyelination

Abstract

Myelination is critical for the normal functioning of the vertebrate nervous system. In the CNS, myelin is produced by oligodendrocytes, and the loss of oligodendrocytes and myelin results in severe functional impairment. Although spontaneous remyelination occurs in chronic demyelinating diseases such as multiple sclerosis, the repair process eventually fails, often resulting in long-term disability. Two distinct general approaches can be considered to promote myelin repair. In one the target is stimulation of the endogenous myelin repair process through delivery of growth factors, and in the second the target is augmentation of the repair process through the delivery of exogenous cells with myelination potential. In both cases, effective treatment of diseases such as multiple sclerosis requires modulation of the immune system, since demyelination is associated with specific immunological activation. Recent studies have shown that some populations of stem cells, including mesenchymal stem cells, have the capacity of promoting endogenous myelin repair and modulating the immune response, prompting an assessment of their use as therapy in demyelinating diseases such as MS. Other types of demyelinating disorders, such as the leukodystrophies, may require multiple repair strategies including both replacement of dysfunctional cells and delivery or supplementation of growth factors, immune modulators or metabolic enzymes. Here we discuss the use of stem cells for the treatment of demyelinating diseases. While the current number of stem cell-based clinical trials for demyelinating diseases is limited, this is likely to increase significantly in the next few years, and a clear understanding of the applicability, limitations and underlying mechanisms mediating stem cell repair is critical.