Effect of FK506 on peripheral nerve regeneration through long grafts in inbred swine.
Numerous small-animal studies have demonstrated that FK506 enhances nerve regeneration and accelerates functional recovery after nerve injury. However, no experimental study has corroborated these neuroregenerative effects in larger animals. This study investigated the effects of FK506 on nerve regeneration in inbred miniature swine. Eight animals received 8-cm ulnar nerve autografts and allografts. Treated animals received 0.1 to 0.4 mg/kg FK506 injections twice weekly to maintain immunosuppressive serum FK506 levels. At 24 weeks posttransplant, nerve grafts were harvested for histomorphometric analysis. Mixed lymphocyte cultures demonstrated alloreactivity in 1 treated animal and all untreated animals. In autografts, mean fiber count, nerve density, and percent neural tissue were doubled with FK506 therapy. In allografts, significant neuroregeneration was observed in animals treated with FK506, whereas untreated animals had no regeneration. Treatment with FK506 resulted in a trend toward enhanced axonal regeneration through nerve autografts and allografts in a large-animal model with defined histocompatibility barriers.
Jensen
John N
JN
Division of Plastic and Reconstructive Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Brenner
Michael J
MJ
Tung
Thomas H
TH
Hunter
Daniel A
DA
Mackinnon
Susan E
SE
D000818:Animals; D017849:Animals, Inbred Strains; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009416:Nerve Regeneration / Q000187:drug effects*; D010525:Peripheral Nerves / Q000187:drug effects*; D013552:Swine; D016559:Tacrolimus / Q000008:administration & dosage / Q000494:pharmacology*; D019737:Transplants
D007166:Immunosuppressive Agents; D016559:Tacrolimus