We have a long-standing interest in repairing myelin defects in the central nervous system (CNS) through transplantation of myelin-producing cells. While this research initially explored the ability of exogenously derived glia to myelinate axons on transplantation into a myelin deficient environment, we are now interested in applying such an approach therapeutically to human myelin disorders. The major target is multiple sclerosis (MS) where the first goal is to remyelinate focal lesions located in strategic areas of the CNS that are critical to clinical function, such as the spinal cord. We also are attempting to apply glial cell transplant therapies to the genetic disorders of myelin such as Pelizaeus Merzbacher disease and Krabbe’s disease. To study repair in these diseases we utilize a range of animal models in which there is failure of myelination (dysmyelination) or where myelin is lost (demyelination) as a consequence of a genetic abnormality. We also use the animal model of MS, experimental allergic encephalomyelitis (EAE), in which there is inflammation, demyelination, and axon loss.

A critical goal that will help lead this experimental work to clinical translation is to identify cells of the oligodendrocyte lineage that could be transplanted and repair areas of myelin absence or loss in the models noted above. We have used oligodendrocyte progenitor cells (OPCs) extensively as derived from free-floating collections of cells known as oligospheres. We have also examined the potential for neural stem cells or embryonic stem (ES) cells to give rise to myelinating cells and this is the subject of on-going studies with our collaborator, Dr. Su-Chun Zhang. A better understanding of the developmental lineage of human oligodendrocytes from ES cells and the cues that are required for this differentiation will be important in isolating sufficient numbers of human oligodendrocytes that can be used for repair purposes.