En-bloc Heart and Thymus Transplantation in Cynomolgus Monkeys

Ashok Muniappan, Douglas R Johnston, Dax A Guenther, Tsuyoshi Shoji, Svjetlan S Boskovic, Ruediger Hoerbelt, Stuart L Houser, James S Allan, Kazuhiko Yamada, Tatsuo Kawai, John C Wain, David H Sachs, Joren C Madsen
Massachusetts General Hospital and Harvard Medical School, Boston, MA

Objective:
To determine whether cotransplantation of a whole vascularized donor thymic lobe can prolong cardiac allograft survival in cynomolgus monkeys. To test this modality in primates and, at the same time, test a procurement technique applicable to human cadaveric heart transplantation, we have developed an en-bloc heart-thymus transplant procedure for cynomolgus monkeys.
Design: The right mediastinal thymus was harvested en-bloc with the heart, preserving the entire arterial supply and venous drainage to the thymus. The en-bloc heart-thymus grafts were transplanted heterotopically into MHC mismatched cynomolgus monkeys. Recipients were treated with rabbit anti-thymocyte globulin at the time of transplant, and daily FK506 for 28 days. Some recipients were thymectomized on the day of transplant.
Results: Three control animals were transplanted with unmodified heart alone (one was thymectomized at the time of transplant). Cardiac allograft survival was 40, 61 (euthymic), and 62 (thymectomized) days. Three animals underwent en-bloc heart-thymus transplantation (one was thymectomized at the time of transplant). En-bloc heart-thymus allograft survival was 158, 48 (euthymic), and 127 (thymectomized) days. Acute rejection was eventually seen in the donor thymus and heart and all animals maintained donor specific responsiveness by MLR.
Conclusions: En-bloc heart-thymus transplantation is technically feasible in non-human primates. Thymic lobe cotransplantation modestly prolonged cardiac allograft survival. The failure to induce stable tolerance by heart-thymus transplantation in this model may be due to compromise of the donor thymus unrelated to surgical technique. We hypothesize that more effective T cell depletion may be required to prevent acute rejection of the donor thymus.

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