The effect of full dose composite tissue allotransplantation immunosuppression on allograft motor nerve regeneration in a rat sciatic nerve model

Background: The purpose of this study was to identify which triple immunosuppressive protocols, currently used for vascularized composite allotransplantation in the clinic, will have the best effect on motor function recovery following nerve allograft reconstruction. Methods: Eighty-eight Lewis rats underwent a 1-cm sciatic nerve allograft transplantation and skin graft from 44 Brown-Norway rats. Group I received 0.9% isotonic saline (control); Group II, 2 mg/kg FK506; Group III, 1 mg/kg FK506 with 15 mg/kg mycophenolate mofetil (MMF); and Group IV, 2 mg/kg FK506 with 30 mg/kg MMF and prednisone. Each group consisted of 11 rats. After 12 weeks, motor function recovery was evaluated with isometric tetanic force, muscle mass, ankle contracture angle, electrophysiology, and nerve histomorphometry. Adequacy of immunosuppression was monitored with the transplanted skin graft. All data are expressed as a percentage of the contralateral side. Results: Isometric tetanic force showed significantly better functional recovery in all groups treated with immunosuppression compared to control. Within the immunosuppression groups no significant difference was found: 42.1 ± 6.4% (Group I), 56.1 ± 12.4% (Group II), 58.4 ± 10.7% (Group III), and 61.3 ± 11.2% (Group IV). Group IV was superior to all other groups regarding ankle contracture (P <.05) and electrophysiology (P <.001). Skin graft rejection occurred in 41 and 0% (Groups III and IV, respectively). Conclusions: FK506 significantly enhanced motor recovery after allograft reconstruction. This effect was comparable between combination treatment (low-dose FK506 and MMF) and triple therapy (high-dose FK506 and MMF plus prednisolone). However, triple therapy was more effective in suppressing skin rejection.