Induction of Schwann Cells from Rat Bone Marrow Mesenchymal Stem Cells

Bone marrow mesenchymal stem cells (BMSCs) are one of mesenchymal stem cells that have been known to exhibit the broad-range differentiation ability, so that their application to cell therapy has been expected. When transplanted into the injured nerve in peripheral and central nervous system (PNS and CNS), Schwann cells support axonal regeneration and re-form myelin sheath to contribute to recovery of neurological function. In the case of Schwann cell transplantation, there are two major difficulties with regard to the source of Schwann cells and obtaining an enough number of cells for grafting. We developed the efficient method to induce BMSCs into functional Schwann cells by using step-by-step treatments of cytokines and reagents. Firstly, BMSCs are treated with beta-mercaptoethanol followed by all-trans-retinoic acid, and finally cells are instructed to differentiate into SCHWANN cells by the combination of forskolin, basic fibroblast growth factor, platelet-derived growth factor and heregulin. Following these treatments, BMSCs gradually change their morphology and express Schwann cell markers in a stepwise manner. Our previous study of one year's observation after transplantation of BMSC-derived Schwann cells to the monkey peripheral nerve injury model revealed the safety and efficacy of the induced Schwann cells. Thus, BMSCs are a realistic source of Schwann cells, and those induced cells are expected to be applied to cell therapy for nerve injury in PNS and CNS.