Adult porcine islet transplantation in baboons treated with conventional immunosuppression or a non-myeloablative regimen and CD154 blockade.

摘要: The aim of the present study was to assess survival adult porcine islets transplanted into baboons receiving either (I) conventional triple drug immunosuppressive therapy or (2) a non-myeloablative regimen and an anti-CD154 monoclonal antibody (mAb) aimed at tolerance-induction. Group 1 (n = 3) were pancreatectomized prior intraportal injection 10,000 islet equivalents (IE)/kg immunosuppressed with anti-thymocyte globulin (ATG), cyclosporine azathioprine. In 2 2), non-pancreatectomized underwent induction whole body thymic irradiation, ATG. Extracorporeal immunoadsorption (EIA) anti-Galalpha1,3Gal (Gal) carried out. Maintenance cobra venom factor, cyclosporine. mycophenolate mofetil, methylprednisolone mAb. Porcine injected intraportally (14,000 32,000 IE/kg, respectively) high-dose pig mobilized peripheral blood progenitor cells (3 x 10(10) cells/kg) infused systemic vein. also implanted in sternomastoid muscle facilitate subsequent biopsies. both groups. C-peptide measured, histological examination liver biopsies performed regular intervals. 1, total pancreatectomy reduccd human 14 days. However, despite depletion T cells, anti-Gal complement, CD154-hlockade, rejected by day 28. These results suggest that powerful innate immune responses are involved rejection discordant xenogencic islets.