Contrast in the efficacy of hDAF mouse hearts between ex vivo perfusion and transplantation into primates

In recent experiments, in which we compared hDAF transgenic rat hearts perf used with 15%, human serum in the Langendorff device and hDAF rat hearts tr ansplanted into cynomolgus monkeys, we demonstrated that in the ex vivo hea rt perfusion model both homozygous and heterozygous hDAF hearts survived lo nger as nontransgenic controls. Surprisingly, we found that only homozygous hDAF hearts were protected against hyperacute rejection in vivo. The first aim of this study was to determine whether perfusion of mouse hearts with higher human serum concentrations or human blood might explain some of the differences found in survival time of the recently performed experiments wi th rat heart xenografts. Secondly, we investigated whether the observed dif ferences in survival times of rat xenografts between in vivo and ex vivo tr ansplantation would also hold for mouse hearts transgenic for hDAF. An ex v ivo model was used to perfuse hDAF mouse hearts and controls with human ser um or blood, and hDAF transgenic hearts and controls were transplanted into cynomolgus monkeys. hDAF transgenic mouse hearts survived significantly lo nger than their controls when perfused with 15% human, serum, but no differ ence was found when 30% human serum was used, or when these hearts were tra nsplanted into cynomolgus monkeys. However, in both the in vivo and ex vivo models the amount of PMNS adhering to the vascular endothelium was signifi cantly lower in hDAF transgenes as compared with their controls. In conclus ion, in the ex vivo situation, the efficacy of hDAF transgenesis in prevent ing HAR is limited by serum complement concentration.