Migration and remyelination by oligodendrocyte progenitor cells transplanted adjacent to focal areas of spinal cord inflammation

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system. Exogenous cell replacement in MS lesions has been proposed as a means of achieving remyelination when endogenous remyelination has failed. However, the ability of exogenous cells to remyelinate axons in the presence of inflammation remains uncertain. We have explored the remyelinating capacity of an oligodendrocyte progenitor cell line CG-4 transduced with the GFP gene and transplanted adjacent to a zymosan-induced focal demyelination model in the rat spinal cord. The resulting zymosan-induced lesions were characterized by persistent macrophage/microglia activation, focal demyelination, degeneration of axons, and reactive astrogliosis. GFP(+) CG-4 cells were found to migrate preferentially toward the inflammatory lesion and survive inside the lesion. A proportion of GFP(+) CG-4 cells differentiated into mature oligodendrocytes and remyelinated axons within the lesion. These findings suggest that grafted oligodendrocyte progenitors may migrate toward areas of inflammation in the adult rat spinal cord, where they can survive and differentiate into myelinating oligodendrocytes.