Neuroregeneration in composite tissue allografts: effect of low-dose FK506 and mycophenolate mofetil immunotherapy.
BACKGROUND
The immunosuppressant FK506 has been reported to increase the rate of peripheral nerve regeneration in nerve crush injury and nerve allograft models. The purpose of this study was to determine whether low doses of FK506 and mycophenolate mofetil had a neuroregenerative effect in revascularized peripheral nerve allografts in a rat hind limb transplantation model.


METHODS
Wistar Furth rat recipients received limbs from syngeneic Wistar Furth donors (group 1, n = 4) or from allogeneic August X Copenhagen Irish rat donors (group 2, n = 6). Wistar Furth recipients received limbs from August X Copenhagen Irish donors and were treated with FK506/mycophenolate mofetil for 5 months (group 3, n = 7). At the end of the follow-up period, histomorphometric analysis of sciatic and tibial nerves from transplanted and intact hind limbs was conducted. Sciatic and tibial nerves were examined at the level of coaptation and near the neuromuscular junction, respectively.


RESULTS
Transplanted limbs in groups 1 and 3 completed the study without rejection, while the limbs in group 2 were rejected within a few days. Sciatic and tibial nerve analysis in groups 1 and 3 limbs showed myelinated axons of various diameters but in significantly fewer numbers than in nontransplanted contralateral nerves. The number and size of myelinated axons of transplanted nerves at corresponding levels were not significantly different between syngeneic and allogeneic (FK506/mycophenolate mofetil-treated) transplants.


CONCLUSIONS
The authors conclude that long-term neuroregeneration of revascularized peripheral nerves using low-dose FK506/mycophenolate mofetil was similar to that of syngeneic transplants. The occurrence of acute rejection episodes with low-dose FK506/mycophenolate mofetil did not appear to benefit nor impair neuroregeneration.
Cottrell
Bradford L
BL
Department of Surgery, Kentucky Spinal Cord Injury Research Center, University of Louisville School of Medicine, USA.
Perez-Abadia
Gustavo
G
Onifer
Stephen M
SM
Magnuson
David S
DS
Burke
Darlene A
DA
Grossi
Federico V
FV
Francois
Cedric G
CG
Barker
John H
JH
Maldonado
Claudio
C
D000714:Anastomosis, Surgical; D000818:Animals; D001369:Axons / Q000648:ultrastructure; D003286:Contracture / Q000209:etiology; D004353:Drug Evaluation, Preclinical; D004359:Drug Therapy, Combination; D005267:Femoral Nerve / Q000098:blood supply / Q000502:physiology* / Q000601:surgery; D005531:Foot Deformities, Acquired / Q000209:etiology; D006084:Graft Rejection / Q000517:prevention & control; D006614:Hindlimb / Q000294:innervation / Q000637:transplantation*; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008866:Microsurgery; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D009186:Myelin Sheath / Q000502:physiology / Q000648:ultrastructure; D009416:Nerve Regeneration / Q000187:drug effects*; D011183:Postoperative Complications / Q000209:etiology; D051381:Rats; D011919:Rats, Inbred Strains; D011920:Rats, Inbred WF; D012584:Sciatic Nerve / Q000098:blood supply / Q000502:physiology* / Q000601:surgery; D013536:Suture Techniques; D016559:Tacrolimus / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D014184:Transplantation, Homologous
D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D016559:Tacrolimus