4.3 Article

Large-gap peripheral nerve repair using xenogeneic transplants in rhesus macaques

Journal

XENOTRANSPLANTATION
Volume 30, Issue 2, Pages -

Publisher

WILEY
DOI: 10.1111/xen.12792

Keywords

peripheral nerve; tacrolimus; Xenotransplantation

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Successful repair of fully transected radial nerves using viable porcine nerves genetically engineered from GalT-KO designated pathogen free (DPF) donors. This transplantation resulted in nerve regeneration, recovery of wrist extension function, and distal muscle reinnervation, demonstrating the safety and efficacy of viable porcine nerve transplants and the potential of xenotransplantation.
Surgical intervention is required to successfully treat severe, large-gap (>= 4 cm) peripheral nerve injuries. However, all existing treatments have shortcomings and an alternative to the use of autologous nerves is needed. Human and porcine nerves are physiologically similar, with comparable dimensions and architecture, presence and distribution of Schwann cells, and conserved features of the extracellular matrix (ECM). We report the repair of fully transected radial nerves in 10 Rhesus Macaques using viable, whole sciatic nerve from genetically engineered (GalT-KO), designated pathogen free (DPF) porcine donors. This resulted in the regeneration of the transected nerve, and importantly, recovery of wrist extension function, distal muscle reinnervation, and recovery of nerve conduction velocities and compound muscle action potentials similar to autologous controls. We also demonstrate the absence of immune rejection, systemic porcine cell migration, and detectable residual porcine material. Our preliminary findings support the safety and efficacy of viable porcine nerve transplants, suggest the interchangeable therapeutic use of cross-species cells, and highlight the broader clinical potential of xenotransplantation.

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