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

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.

Vital, Porcine, Gal-Knockout Skin Transplants Provide Efficacious Temporary Closure of Full-Thickness Wounds: Good Laboratory Practice-Compliant Studies in Nonhuman Primates.

Vital, genetically engineered porcine skin transplants have long been regarded as a promising treatment option for severe burn wounds. The objective of this two-part, preclinical study was to evaluate the ability of vital, split-thickness skin xenotransplants derived from designated pathogen-free, alpha 1,3 galactosyltransferase knockout miniature swine to provide temporary wound closure of full-thickness wound defects intended to model severe and extensive, deep partial- and full-thickness burn wounds. In part 1 of the study, four full-thickness wound defects were introduced in four cynomolgus macaques recipients and, then engrafted with two xenografts and two allografts to achieve temporary wound closure. On POD-15, autografts were used to achieve definitive wound closure and were observed until POD-22. In part 2 of the study, four additional subjects each received two full-thickness wound defects, followed by two xenografts to achieve temporary wound closure, and were observed postoperatively for 30 days without further intervention. All grafts were assessed for signs of adherence to the wound bed, vascularity, and signs of immune rejection via gross clinical and histological methods. Xenograft and allograft comparators were equivalent in part 1, and later autografts were otherwise indistinguishable. In part 2, all xenotransplants demonstrated adherence, vascularity, and survival until POD-30. These were unexpected results that exceed previously published findings in similar models. Furthermore, the ensuing GLP-study report directly supported regulatory clearance, permitting a phase I clinical trial. This solution holds great promise as an alternative to human cadaver allograft, the current standard of care for the treatment of severe burns.