A new strategy for prolonging xenograft survival

A new strategy based on a clonal reduction hypothesis has been developed for prolonging concordant cardiac xenograft survival. Splenocytes from Golden Syrian hamsters were transfused intravenously into Lewis rats 14 days before the time of a donor-specific heart transplant into the recipient. Cyclophosphamide was administered from days -11 to -7 to reduce or eliminate proliferating xenoreactive clones. Low dose CsA was administered after the cyclophosphamide to prevent emergence and expression of xenoreactive cells. Finally, rapamycin 1.0 mg/kg was given for 5 days after transplant as further immunosuppression since it acts synergistically with CsA. In the group that received no immunosuppression after day +8, mean graft survival was 33.2 +/- 7.0 days with 10 of 17 xenografts surviving > 28 days. Extending either CsA therapy or rapamycin therapy after day +8 did not prolong graft survival. Each component of the therapy was found to be necessary for the effect.