Successful nerve regeneration is critical to the functional success of composite tissue allografts. The present study was designed to characterize the effect of acute rejection on nerve regeneration and functional recovery in the setting of orthotopic limb transplantation.
A rat orthotopic limb transplantation model was used to evaluate the effects of acute rejection on nerve regeneration and motor recovery. Continuous administration of FK506 (full suppression), administration of FK506 for the first 8 of 12 weeks (late rejection), or delayed administration of FK506/dexamethasone following noticeable rejection (early rejection) was used to preclude or induce rejection following limb transplantation. Twelve weeks postoperatively, nerve regeneration was assessed by means of histomorphometric analysis of explanted sciatic nerve, and motor recovery was assessed by means of evoked muscle force measurement in extensor digitorum longus muscle.
A single episode of acute rejection that occurs immediately or late after reconstruction does not significantly alter the number of regenerating axonal fibers. Acute rejection occurring late after reconstruction adversely affects extensor digitorum longus muscle function in composite tissue allografts.
Collected data reinforce that adequate immunosuppressant administration in cases of allogeneic limb transplantation ensures levels of nerve regeneration and motor functional recovery equivalent to that of syngeneic transplants. Prompt rescue following acute rejection was further demonstrated not to significantly affect nerve regeneration and functional recovery postoperatively. However, instances of acute rejection that occur late after reconstruction affect graft function. In total, the present study begins to characterize the effect of immunosuppression regimens on nerve regeneration and motor recovery in the setting of composite tissue allografts.
St. Louis, Mo.
From the Division of Plastic and Reconstructive Surgery, Washington University School of Medicine, and the Department of Biomedical Engineering, Washington University in St. Louis.
Received for publication April 30, 2012; accepted September 27, 2012.
Presented in part at the 56th Annual Meeting of the Plastic Surgery Research Council, in Louisville, Kentucky, April 28 through 30, 2011.
Disclosure:The authors have no financial interest to declare in relation to the content of this article.
This work was supported by THE PLASTIC SURGERY FOUNDATION.
Philip J. Johnson, Ph.D.; Division of Plastic and Reconstructive Surgery, Washington University School of Medicine, 660 South Euclid, Campus Box 8238, St. Louis, Mo. 63110, email@example.com