Stable derivation of Schwann cells from human bone marrow stromal cells

Abstract

BACKGROUND. Schwann cell transplantation improves post-traumatic nerve regeneration in both peripheral nervous system (PNS) and central nervous system (CNS) but sufficient numbers of immunocompatible cells are required for clinical application. Bone marrow stromal cells (BMSCs) are a readily accessible cell source that can be expanded and differentiated to specialized cells for regenerative medicine. OBJECTIVES. We attempted to establish a protocol to induce the stable differentiation of human BMSC along a Schwann cell lineage. METHODS. Neurosphere medium was used to induce human BMSCs into neurospheres. Then, these neurospheres were induced to differentiate along the Schwann cell lineage using glia growth factors, and this was followed by co-culture with dorsal root ganglion (DRG) neurons. RESULTS. A lot of spheres of floating cells appeared after human BMSCs were cultured in neurosphere differentiation medium. These BMSCs-induced neuropheres showed nestin- and GFAP-immunoreactive staining. After induction with Schwann cell differentiation medium, a number of bi-polar and spindle-like cells positive for p75 and S100 grew from the neurospheres. However, these Schwann cell-like cells lost their Schwann cell phenotype after the induction medium was changed. Following co-culture with the DRG neurons, all derivatives of the Schwann cell-like cells not only acquired the Schwann cell phenotype, but remained stably committed even in subcultures in which both extrinsic factors and neurons were withdrawn. CONCLUSION. Our success with stable derivation of Schwann cells from human BMSCs offer a viable source of Schwann cells for autologous cell therapy in clinical applications.