Long-term outcome of the repair of 50 mm long median nerve defects in rhesus monkeys with marrow mesenchymal stem cells-containing, chitosan-based tissue engineered nerve grafts

Despite great progress in the fields of tissue engineering and stem cell therapy, the translational and preclinical studies are required to accelerate the clinical application of tissue engineered nerve grafts, as an alternative to autologous nerve grafts, for peripheral nerve repair. Rhesus monkeys (non-human primates) are more clinically relevant and more suitable for scaling up to humans as compared to other mammalians. Based on this premise, and considering a striking similarity in the anatomy and function between human and monkey hands, here we used chitosan/PLGA-based, autologous marrow mesenchymal stem cells (MSCs)-containing tissue engineered nerve grafts (TENGs) for bridging a 50-mm long median nerve defect in rhesus monkeys. At 12 months after grafting, locomotive activity observation, electrophysiological assessments, and FG retrograde tracing tests indicated that the recovery of nerve function by TENGs was more efficient than that by chitosan/PLGA scaffolds alone; histological and morphometric analyses of regenerated nerves further confirmed that the morphological reconstruction by TENGs was close to that by autografts and superior to that by chitosan/PLGA scaffolds alone. In addition, blood test and histopathological examination demonstrated that TENGs featured by addition of autologous MSCs could be safely used in the primate body. These findings suggest the efficacy of our developed TENGs for peripheral nerve regeneration and their promising perspective for clinical applications.