Facial subunit composite tissue allografts in nonhuman primates: I. Technical and immunosuppressive requirements for prolonged graft survival.
BACKGROUND
Widespread application of composite tissue allotransplantation has been impeded by risks of rejection and conventional immunosuppression. The authors have developed a nonhuman primate composite tissue allotransplantation model that demonstrated reliable and long-term success necessary to progress to preclinical studies.


METHODS
Composite facial subunits (e.g., skin, muscle, and bone) were transplanted between mismatched cynomolgus monkeys. Vascular supply was based on the common carotid artery and external and internal jugular veins. Facial allografts were heterotopically transplanted to the recipient's lower abdomen with end-to-side anastomoses of the common carotid artery to the common femoral artery and of both the internal and external jugular veins to the common femoral vein. Animals received tacrolimus monotherapy. Grafts were inspected daily, submitted to biopsy regularly, and studied with magnetic resonance imaging.


RESULTS
Thirteen transplants were performed. Two grafts based on the common carotid artery and only the internal jugular vein failed within 3 to 5 days because of venous thrombosis not related to rejection. Subsequent transplants included anastomoses of both the internal and external jugular veins to the common femoral vein without thromboses. Immunosuppression consisted of tacrolimus monotherapy and was tolerated without complications. Long-term success was achieved with rejection-free graft survival (60 to 177 days).


CONCLUSIONS
The authors have developed the first successful model of facial composite tissue allotransplantation in a nonhuman primate. Technical requirements include preservation of both internal and external jugular venous outflow. Tacrolimus monotherapy permitted prolonged rejection-free graft survival without early complications. This model provides a platform for further investigation of composite tissue allotransplantation tolerance and requirements for indefinite survival.
Barth
Rolf N
RN
Baltimore, Md. From the Division of Transplantation, Department of Surgery; Plastic, Reconstructive, and Maxillofacial Surgery, R Adams Cowley Shock Trauma Center; and Program for Comparative Medicine, University of Maryland School of Medicine.
Bluebond-Langner
Rachel
R
Nam
Arthur
A
Stanwix
Matthew
M
Shipley
Steven
S
Bartlett
Stephen T
ST
Rodriguez
Eduardo D
ED
D000714:Anastomosis, Surgical; D000818:Animals; D016025:Bone Transplantation / Q000379:methods*; D017536:Carotid Artery, Common / Q000000981:diagnostic imaging / Q000601:surgery; D005145:Face / Q000098:blood supply / Q000601:surgery*; D005152:Facial Muscles / Q000637:transplantation*; D005260:Female; D005268:Femoral Vein / Q000637:transplantation; D006084:Graft Rejection / Q000188:drug therapy / Q000517:prevention & control*; D006085:Graft Survival; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007601:Jugular Veins / Q000000981:diagnostic imaging / Q000601:surgery; D008252:Macaca fascicularis; D018810:Magnetic Resonance Angiography; D008297:Male; D023421:Models, Animal; D011859:Radiography; D016038:Skin Transplantation / Q000379:methods*; D016559:Tacrolimus / Q000494:pharmacology; D014184:Transplantation, Homologous
D007166:Immunosuppressive Agents; D016559:Tacrolimus