Ex vivo generation of myelinating Schwann-cell-like cells from bone marrow-derived neurospheres

Abstract

Schwann cell transplantation can promote axonal regrowth and remyelination following spinal cord injury. It is however difficult to obtain sufficient numbers of immunocompatible cells for clinical application. Attempts were therefore made to direct differentiation of myelinating Schwann cell-like cells from marrow stromal cells (MSC). Rat femur MSCs were harvested by selective adherence to tissue culture plastic. The isolated cells were characterized by induction along osteogenic, chondrogenic and adipogenic lineages as well as staining for STRO-1 immunopositivity. Sphere-forming MSCs were then stimulated with Forskolin, bFGF, PDGF and Heregulin to acquire the Schwann-cell-like phenotype. The phenotype was however transient and cells acquired fibroblastic phenotype in extended cultures. In cocultures with dorsal root ganglion neurons, the Schwann-cell like cells stably expressed the markers, S100β and p75, without exogenous growth factors; they aligned with axonal bundles that radiated from the neurons and indicated immunopositivity for myelin basic protein. Functionally stable MSC-derived Schwann cells will then be suitable candidates for autologous transplantation into the injured cord following a period of ex-vivo induction.