Cotransplantation of Glial Restricted Precursor Cells and Schwann Cells Promotes Functional Recovery after Spinal Cord Injury

Abstract

Oligodendrocyte (OL) replacement can be a promising strategy for spinal cord injury (SCI) repair. However, the poor posttransplantation survival and inhibitory properties to axonal regeneration are two major challenges that limit their use as donor cells for repair of CNS injuries. Therefore, strategies aimed at enhancing the survival of grafted oligodendrocytes as well as reducing their inhibitory properties, such as the use of more permissive oligodendrocyte progenitor cells (OPCs), also called glial restricted precursor cells (GRPs), should be highly prioritized. Schwann cell (SC) transplantation is a promising translational strategy to promote axonal regeneration after CNS injuries, partly due to their expression and secretion of multiple growth-promoting factors. Whether grafted SCs have any effect on the biological properties of grafted GRPs remains unclear. Here we report that either SCs or SC-conditioned medium (SCM) promoted the survival, proliferation, and migration of GRPs in vitro. When GRPs and SCs were cografted into the normal or injured spinal cord, robust survival, proliferation, and migration of grafted GRPs were observed. Importantly, grafted GRPs differentiated into mature oligodendrocytes and formed new myelin on axons caudal to the injury. Finally, cografts of GRPs and SCs promoted recovery of function following SCI. We conclude that cotransplantation of GRPs and SCs, the only two kinds of myelin-forming cells in the nervous system, act complementarily and synergistically to promote greater anatomical and functional recovery after SCI than when either cell type is used alone.