Rapid and efficient generation of neural progenitors from adult bone marrow stromal cells by hypoxic preconditioning

Abstract

Schwann cell transplantation promotes post-traumatic regeneration in the CNS and PNS. Neural progenitors enriched from adult bone marrow stromal cell (BMSCs) can be directed to differentiate into Schwann cells, representing a readily accessible source for autologous cell-based therapy. It is essential from a translational standpoint to achieve means of enriching for neural progenitors within these niches. In this current study, we demonstrate that transient culture of rat and human BMSCs in hypoxic conditions (1% for 24 hrs) significantly increases the numbers of neural progenitors. Following on, we identify that hypoxic treatment induced up-regulation of EGF receptor (EGFR) in BMSCs. Addition of EGFR inhibitor while cells are cultured in hypoxic condition largely abolished this increase in neural progenitor production. As a proof of principle that these neural progenitors can generate mature cells for transplantation purposes, neural progenitors generated from hypoxic treatment were able to differentiate into myelin-forming Schwann cells. Our findings provide a potential means of generating increased numbers of neural cell derivatives from the adult bone marrow, and potentially other niches, for the purpose of nerve injury repair.