Purpose: Vascularized composite allotransplantation (VCA) has demonstrated clinical success with standard immunosuppressive strategies in face, hand, and forearm transplantations. We developed a non-human primate model of thymus-sternum VCA to address technical feasibility, immune tolerance strategies, and presence of chimerism.

Methods: Vascularized thymus-sternal allotransplantations were performed between MHC-mismatched rhesus monkeys (feasibility studies) and baboons (long-term survival studies). A 5-10 cm vascularized anterior chest wall (“sternal”) segment was recovered from a male donor in continuity with associated skin, muscle, thymus, and pericardium. Bilateral internal thoracic and subclavian vessels, ascending aorta and superior vena cava (SVC) were included en bloc in the allograft. For survival studies, a male allograft was transplanted to a female's lower abdominal wall with end-to-side anastomoses of the donor aorta and SVC to the recipient common femoral vessels. In survival studies clinically applicable immunosuppression was given. Skin biopsies and immunological assays were completed at regular intervals and for evidence of skin graft rejection. Presence of chimerism was quantified using polymerase chain reaction specific for baboon Y chromosome.

Results: Four successful transplants were performed, two in the survival model. Survival baboon #1 developed clinical and histologic evidence of acute rejection on days 6 and 77. Day 6 rejection episode resolved with antithymocyte globulin bolus and increase in steroids. Animal #2 developed graft swelling and wound dehiscence on day 8, and the allograft was eventually explanted on day 13 due to progressive wound infection. The animal #2 allograft was viable at the time of explant. Flow cytometry analysis demonstrated complete CD40 receptor blockade. Animal #1 showed transient microchimerism in peripheral blood until day 10 (0.02 to 0.37%), as did animal #2 until day 5 (0.02 to 0.09%).

Conclusion: Vascularized thymus-sternal allotransplantation is technically feasible. Conditions necessary to establish durable macrochimerism and tolerance based on primarily vascularized donor bone and thymus can be explored in this model.

CITATION INFORMATION: O'Neill N, Sendil S, Zhao Y, Hershfield A, Tatarov I, Braileanu G, Hassanein W, Parsell D, Azimzadeh A, Burdorf L, Pierson R, Nam A. Development of a Vascularized Thymus-Sternum Composite Tissue Allograft Model in Non-Human Primates. Am J Transplant. 2016;16 (suppl 3).

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