Large-gap Peripheral Nerve Repair Using Xenogeneic Transplants in Primates

Abstract

\n Early surgical intervention is required to successfully treat severe, large-gap peripheral nerve injuries. However, all existing treatments have shortcomings, and for large-gap injuries (≥4 cm), there is no reported alternative to autologous nerve. We report preclinical repair of large (4 cm), complete transectional radial nerve damage in Rhesus macaques using viable, whole sciatic nerve from genetically engineered, designated pathogen free porcine donors. Porcine nerves are physiologically similar to human nerves, contain neurotrophic growth factors and a matrix-rich scaffold, and offer greater clinical availability. We demonstrate regeneration of the transected nerve, distal muscle reinnervation, and recovery of conduction velocity and compound muscle action potential across xenogeneic transplants resulting in functional recovery comparable to autologous controls. We also show the lack of systemic porcine cell migration and the elimination of detectable transplanted porcine tissue. Our findings support the safety and efficacy of neural porcine therapeutics and the broader clinical potential of xenotransplantation.