Combined Transplantation of Mesenchymal Progenitor and Neural Stem Cells to Repair Cervical Spinal Cord Injury

Mesenchymal progenitor cells (MPC) are effective in reducing tissue loss, preserving white matter, and improving forelimb function after a spinal cord injury (SCI). We proposed that by preconditioning the mouse by the intravenous delivery (IV) of MPCs for 24 h following SCI, this would provide a more favorable tissue milieu for an NSC intraspinal bridging transplantation at day three and day seven. In combination, these transplants will provide better anatomical and functional outcomes. The intravenous MSCs would provide cell protection and reduce inflammation. NSCs would provide a tissue bridge for axonal regeneration and myelination and reconnect long tract spinal pathways. Results showed that initial protection of the injury site by IV MPCs transplantation resulted in no increased survival of the NSCs transplanted at day seven. However, integration of transplanted NSCs was increased at the day three timepoint, indicating MPCs influence very early immune signaling. We show, in this study, that MPC transplantation resulted in a co-operative NSC cell survival improvement on day three post-SCI. In addition to increased NSC survival on day three, there was an increase in NSC-derived mature oligodendrocytes at this early timepoint. An in vitro analysis confirmed MPC-driven oligodendrocyte differentiation, which was statistically increased when compared to control NSC-only cultures. These observations provide important information about the combination, delivery, and timing of two cellular therapies in treating SCI. This study provides important new data on understanding the MPC inflammatory signaling within the host tissue and timepoints for cellular transplantation survival and oligodendroglia differentiation. These results demonstrate that MPC transplantation can alter the therapeutic window for intraspinal transplantation by controlling both the circulating inflammatory response and local tissue milieu.