Towards remyelination therapy with oligodendrocyte precursor derivation from bone marrow stromal cells

Abstract

Myelin damage and disorders caused by physical injury or diseases like leukodystrophies 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 cultured as non-adherent spheres until they expressed markers of neural/glial progenitors. The neural/glial progenitors were then maintained in adherent culture supplemented with β-heregulin, PDGF-AA and bFGF. Oligodendrocyte precursors expressing the markers - NG2, Olig2, PDGFRa and Sox10, were detectable within 2 weeks and can be expanded in culture for up to 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 neurites, 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.