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

Author:

Holzer Paul12,Chang Elizabeth J.2ORCID,Rogers Kaitlyn2ORCID,Tarlton Jamie3ORCID,Lu Diana2,Gillespie Natasha3,Adkins Jon2,Metea Monica4,LaRochelle Alan5,Wicks Joan6,Onel Buket7,Gullans Steve2,Doloff Joshua C.18,Scobie Linda3ORCID,Cetrulo Curtis L.910,Monroy Rod2

Affiliation:

1. Whiting School of Engineering Johns Hopkins University Baltimore Maryland USA

2. XenoTherapeutics Inc. Boston Massachusetts USA

3. Department of Biological and Biomedical Sciences Glasgow Caledonian University Glasgow UK

4. Preclinical Electrophysiology Consulting LLC Boston Massachusetts USA

5. Biomedical Research Models Inc. (Biomere) Worcester Massachusetts USA

6. StageBio Mt Jackson Virginia USA

7. Xeno Diagnostics LLC Indianapolis Indiana USA

8. Department of Biomedical Engineering, Translational Tissue Engineering Center Johns Hopkins University School of Medicine Baltimore Maryland USA

9. Reconstructive Transplantation Laboratory Massachusetts General Hospital Boston Massachusetts USA

10. Shriners Hospital for Children‐Boston Harvard Medical School Boston Massachusetts USA

Abstract

AbstractSurgical 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.

Publisher

Wiley

Subject

Transplantation,Immunology

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