Background: Vascularized composite allografts (VCA) containing vascularized bone marrow (VBM) prolong graft survival. To help elucidate this protective immunomodulatory effect, we irradiated donor facial VCA + VBM with low dose non-myeloblative radiation preoperatively to determine whether immunologic outcomes depended on a radiosensitive donor cell population.

Methods: Facial VCA + VBM segments were heterotopically transplanted to MHC mismatched recipient cynomolgus macaques (n=4) after facial irradiation (1.5 Gy, Pantak HF-320 x-ray system) on POD -1. Immunosuppression consisted of tacrolimus and mycophenolate mofetil without steroid or depletional therapy. End points were determined by severe clinical and pathological rejection of the graft. Flow cytometry using informative donor specific antibodies was utilized to assess chimerism.

Results: All recipients underwent early graft loss (mean 32 ±21 days) from progressive rejection (Banff IV), in 3 animals end points were at 14, 14, and 44 days; and one animal reached end point at day 56 (Banff II) due to malignancy. Peripheral blood chimerism was undetectable with the exception of one animal with 1% chimerism at 14 days. This compared to historical controls of non-irradiated grafts with a mean survival of 348 ±86 days (rejection only after immunosuppression withdrawal), and 3 of 4 demonstrating chimerism. Donor VCA marrow also showed greater recipient replacement, 50% and 70% recipient cells in two animals and complete replacement in the other two animals.

Conclusions: Irradiation of donor facial VCA + VBM graft results in early progressive rejection, decreased chimerism, and marrow replacement by recipient cells. These data support that a radiosensitive cell population confers an immunoprotective effect. We hypothesize that inhibition of a donor cell population within the VBM component decreases mixed chimerism and prevents regulatory interaction between donor and recipient cells.

CITATION INFORMATION: Uluer M, Woodall J, Hassanein W, Drhu U, Bojovic B, Nam A, Bartlett S, Barth R. Radiosensitive Cell Population Prolongs Graft Survival of Vascularized Composite Allografts in Non-Human Primates. Am J Transplant. 2016;16 (suppl 3).

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