Splenectomy improves survival of hDAF transgenic pig kidneys in primates
Schmoeckel M., Bhatti E., Zaidi A., Cozzi E., Pino-Chavez G., Wallwork J., White D., Friend P.
The production of transgenic pigs expressing a human regulator of complement activation (decay accelerating factor, hDAF) has allowed to abrogate hyperacute rejection after organ transplantation into primates and to achieve prolonged survival. In this study hDAF transgenic porcine kidneys were transplanted into cynomolgus monkeys in a life-supporting model (the native kidneys were removed). Immunosuppression consisted of an induction therapy with cyclophosphamide and maintenance with cyclosporin A, mycophenolate mofetil and steroids. The additional effect of concomitant splenectomy was investigated in a second group. Splenectomy prolonged survival from 17 days to 43 days (median) without any effect on the incidence of rejection. In the absence of rejection episodes transgenic kidneys maintained normal serum homeostasis and fluid balance. Improved immunosuppressive combinations may enable long-term survival of transgenic kidneys in primates in the near future.