Towards remyelination therapy: derivation of oligodendrocyte precursors from adult bone marrow stromal cells

Abstract

Myelin damage and disorders cause axon to degenerate and result in severe loss of function. With an aim towards remyelination therapy, we attempted to direct differentiation of bone marrow stromal cells (BMSCs, adult rats) along the oligodendroglial lineage in vitro. BMSCs were first maintained in non-adherent culture to derive spheres of neural progenitors. These BMSC-derived neural progenitors were then induced to differentiate along oligodendorglial lineage in adherent culture supplemented with β-heregulin, PDGF-AA and bFGF. Oligodendrocyte precursors expressing the markers - NG2, Olig2, PDGFRa and Sox10, were detectable within two weeks and can be expanded in culture for more than 3 months with no observable decline in marker expression. To test for myelination capability, BMSC-derived oligodendrocyte precursor cells (OPCs) in a 2-week co-culture with dorsal root ganglion neurons extended myelin basic protein-positive processes along axons, suggesting maturation into myelinating oligodendrocytes. In vivo myelination by BM-OPCs was tested by exploitation of unmyelinated axons of retinal ganglion cells of adult rats. Myelin basic protein-positive processes were also observable along retinal axons by 8 weeks post-injection. Our findings indicate BMSCs as a possible source of OPCs for remyelination therapy.