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

Abstract

Loss of myelin due either to congenital abnormalities or traumatic injuries impacts on conduction of nerve impulses, causing neurological deficits. Our recent success with a strategy that enriches and expands the neural progenitor subpopulation among adult samples of bone marrow stromal cells provided impetus for pursuit of bone marrow-derived neural progenitors (BM-NPs) as source for deriving oligodendrocyte precursors (OPs) for use in transplantation and remyelination. Cultures of rat BM-NPs treated with supplements of β-heregulin, PDGF-AA and bFGF fostered the derivation of oligodendrocyte precursors in 3 weeks. These BM-OPs were positive for the OP markers, NG2, Olig2, PDGFRα and Sox10. The BM-OPs were then subjected to in vitro myelination assay in co-cultures with purified DRG neurons. In 2 weeks, BM-OPs matured into oligodendrocytes and extended myelin basic protein-positive processes along multiple neurites. The BM-OPs were further transplanted into the corpus callosum of myelin-deficient, juvenile Shiverer mice. Mature oligodendrocytes and ultrastructure of compact myelin were identifiable in the corpus callosum in 6 weeks. Our findings indicate BMSCs as a possible source of oligodendrocyte precursors for CNS remyelination therapy.