In vitro derivation of oligodendrocyte precursors from neural progenitors harbored in the adult bone marrow--implications for remyelination therapy

Abstract

Transplantation of oligodendrocyte prcursors (OPs) into the CNS represents a means to promote remyelination in cases where the endogenous capacity for myelination is limited. In search of a safe and accessible source of OPs, we used the adult rat as model and identified neural progenitors harboured in bone marrow stromal cells (BMSCs). The neural progenitor population was selectively expanded in non-adherent, sphere-forming cultures of the BMSCs. The resulting BMSC-derived neural progenitors were then directed to differentiate into OPs in adherent culture. The BMSC-derived OPs were positive for such markers as Olig2, NG2, Sox10 and PDGFR-alpha. They differentiated into myelin basic protein (MBP)-expressing oligodendrocytes following co-culture with purified dorsal root ganglion neurons. Following transplantation into the corpus callosum of myelin-deficient shiverer mice, the BMSC-derived OPs differentiated into functionally mature oligodendrocytes showing the capacity to form compact myelin. BMSCs therefore constitute an accessible and expandable source of neural progenitors for OP derivation and hence cell replacement therapy in CNS injury and demyelination disorders. (Supported by HMRF 05163156)