Scar tissue removal-activated endogenous neural stem cells aid Taxol-modified collagen scaffolds in repairing chronic long-distance transected spinal cord injury

Abstract

Scar tissue removal combined with biomaterial implantation is considered an effective measure to repair chronic transected spinal cord injury (SCI). However, whether more scar tissue removal surgeries could affect the treatment effects of biomaterial implantation still needs to be explored. In this study, we performed the first scar tissue removal surgery in the 3^rd month and the second in the 6^th month after completely removing 1 cm of spinal tissue in canines. We found that Taxol-modified linear ordered collagen scaffold (LOCS + Taxol) implantation could promote axonal regeneration, neurogenesis, and electrophysiological and functional recovery only in canines at the first scar tissue removal surgery, but not in canines at the second scar tissue removal surgery. Interestingly, we found that more endogenous neural stem cells (NSCs) around the injured site could be activated in canines with the first rather than the second scar tissue removal. Furthermore, we demonstrated that Taxol could promote the neuronal differentiation of NSCs in the myelin inhibition microenvironment through the p38 MAPK signaling pathway in vitro. Therefore, we speculated that endogenous NSC activation by the first scar tissue removal surgery and its further differentiation into neurons induced by Taxol may contribute to functional recovery in canines. Together, LOCS + Taxol implantation in combination with the first scar tissue removal provides a promising therapy for chronic long-distance transected SCI repair with the help of scar tissue removal activated endogenous NSCs.