Long-term discordant xenogeneic (porcine-to-primate) bone marrow engraftment in a monkey treated with porcine-specific growth factors

Background. Mixed allogeneic hematopoietic chimerism has previously been re liably achieved and shown to induce tolerance to fully MHC-mismatched allog rafts in mice and monkeys. However, the establishment of hematopoietic chim erism has been difficult to achieve in the discordant pig-to-primate xenoge neic model. Methods. To address this issue, two cynomolgus monkeys were conditioned by whole body irradiation (total dose 300 cGy) 6 and 5 days before the infusio n of pig bone marrow (BM), Monkey anti-pig natural antibodies were immunoad sorbed by extracorporeal perfusion of monkey blood through a pig liver, imm ediately before the intravenous infusion of porcine BM (day 0). Cyclosporin e was administered for 4 weeks and 15-deoxyspergualin for 2 weeks. One monk ey received recombinant pig cytokines (stem cell factor and interleukin 3) for 2 weeks, whereas the other received only saline as a control. Results. Both monkeys recovered from pancytopenia within 4 weeks of whole b ody irradiation. Anti-pig IgM and IgG antibodies were successfully depleted by the liver perfusion but returned to pretreatment levels within 12-14 da ys. Methylcellulose colony assays at days 180 and 300 revealed that about 2 % of the myeloid progenitors in the BM of the cytokine-treated recipient we re of pig origin, whereas no chimerism was detected in the BM of the untrea ted control monkey at similar times. The chimeric animal was less responsiv e by mixed lymphocyte reaction to pig-specific stimulators than the control monkey and significantly hyporesponsive when compared with a monkey that h ad rejected a porcine kidney transplant. Conclusion. To our knowledge, this is the first report of long-term surviva l of discordant xenogeneic BM in a primate recipient.