Effect of surrogate tolerogenesis on the vascular rejection of pig heart xenografts

Background, Organ xenografts are fulminantly rejected by antibody-mediated vascular rejection. Surrogate tolerogenesis (ST), the induction of toleranc e within the donor, is effective with aorta xenografts, This preliminary st udy assesses the effect of ST on preformed antibodies and rejection of porc ine heart xenografts, Methods. Tolerance to the donor pig was induced by infusing recipient marro w into fetal pigs, Later, pig splenocytes were transfused and heterotopic p ig hearts transplanted using chimeric or nonchimeric pigs, Anti-pig antibod ies were assessed. Results. With ST alone, xenografts developed cellular rejection at 4-6 days , whereas control grafts developed vascular rejection at 3-4 days (cellular vs. vascular, P<0.03). There was a reduction in preformed antibodies (P<0. 03). ST combined with moderate cyclosporine prevented rejection at 9+ and 2 5 days in sensitized recipients compared with vascular rejection at 0.5-2 d ays for controls (P<0.07). Conclusions. ST seems to provide protection against vascular rejection. The cellular rejection seems sensitive to cyclosporine.