The Effects of Growth Hormone on Nerve Regeneration and Alloimmunity in Vascularized Composite Allotransplantation.

Abstract

Background: Poor outcomes in functional recovery following upper extremity transplantation are largely due to denervation-induced muscle atrophy that occurs during the prolonged period of nerve regeneration. Growth hormone (GH) has well-established trophic effects on neurons, myocytes, and Schwann cells and represents a promising therapeutic approach to address this challenge. This study sought to confirm the positive effects of GH treatment on nerve regeneration and functional recovery and to evaluate the effects of GH treatment on the immune response in the setting of vascularized composite allotransplantation. Methods: Rats underwent orthotopic forelimb transplantation across a full MHC-mismatch and received either porcine-derived growth hormone or no treatment (n=18 per group). Functional recovery was measured using electrically-stimulated grip strength testing. Animals were monitored for clinical and subclinical signs of rejection. Results: Neuromuscular junction reinnervation and grip strength were improved in GH-treated animals (p=0.005; p=0.08). No statistically significant differences were seen in muscle atrophy, degree of myelination, axon diameter, and axon counts between groups. The rates of clinical and histological rejection did not significantly differ among groups. Conclusions: Our findings alleviate concern for increased risk of transplant rejection during GH therapy and therefore support the translation of growth hormone as a therapeutic method to promote improved functional recovery in upper extremity transplantation.