A Novel Model for Evaluating Nerve Regeneration in the Composite Tissue Transplant: The Murine Heterotopic Limb Transplant

Abstract

For individuals who have experienced debilitating upper extremity injury or amputation, hand transplantation holds the potential for drastic quality of life improvement. This potential depends on adequate nerve regeneration into the transplant and reanimation of graft musculature. In this study, we demonstrate the use of a murine heterotopic limb transplant model for evaluation of nerve regeneration in a composite tissue allograft (CTA). We also compare the effects of various immunosuppressive regimens on nerve regeneration in this model. The study consisted of five groups of mice, all of which underwent heterotopic limb transplant with coaptation of the recipient and donor sciatic nerves. The groups received the following immunosuppressive regimens: group A (positive control)-syngeneic transplant, no immunosuppression; group B (negative control)-allogeneic transplant, no immunosuppression; group C-allogeneic transplant, FK-506 + MR1; group D-allogeneic transplant, MR1 + CTLA4-Ig; group E-syngeneic transplant, FK-506 treatment with preloading. Group B animals showed signs of transplant rejection as early as 5days postoperatively. Except for one mouse from group C and one mouse from group D, all other animals had viable transplants and nerve regeneration present in the donor sciatic nerve at the 3-week endpoint of the study. To our knowledge, this represents the first report of the use of a mouse CTA model for evaluation of nerve regeneration. The mouse heterotopic limb transplant model will be a valuable tool for CTA research since it can be performed with more ease, and with less host morbidity and mortality than the mouse orthotopic model.