Towards remyelination therapy with oligodendrocyte precursor and Schwann cells derived from bone marrow stromal cells

Abstract

Myelin damage and disorders caused by injuries or diseases result in neuronal death and severe loss of function. With an aim to generate peripheral and central glial cells for remyelination therapy, we attempted to direct differentiation of bone marrow stromal cells (BMSCs, adult rats) along the oligodendroglial and Schwann cell lineages in vitro. BMSCs were maintained in sphere cultures until they expressed markers of neural progenitors. Then adherent culture supplemented with β-heregulin, PDGF-AA and bFGF induced differentiation of sphere cells into oligodendrocyte precursors (positive for NG2, Olig2, PDGFRa and Sox10). Alternatively, coculture of sphere cells with purified dorsal root ganglia (DRG) neurons in adherent culture supplemented with β-heregulin, PDGF-AA, bFGF and forskolin yielded fate-committed Schwann cells (positive for p75 and S100β). We hypothesize therefore that signals from DRG neurons switched the neural progenitors from the oligodendroglial fate to the Schwann cell fate. Myelinating function of these BMSC-derived glial cells was tested in co-culture with purified DRG neurons. In 2 weeks of coculture, BM-OPCs matured into oligodendrocytes and extended myelin basic protein (MBP)-positive processes along multiple axons. Vitamin C was required in the coculture with BM-SchCs for alignment with axons to develop into MBP-positive myelinated internodes. Our findings indicate BMSCs as a possible source of both OPCs and Schwann cells for remyelination therapy. [HKRGC GRF 777810M]