Long-term survival of donor-specific pancreatic islet xenografts in fully xenogeneic chimeras (F344 rat to B10 mouse).

THE development of procedures to isolate large numbers of purified human pancreatic islet cells has made it possible to initiate a new phase of clinical trials in pancreatic islet transplantation for treatment of type 1 diabetes. 1-3 Although nonspecific immunosuppressive agents have been instrumental in controlling alloreactivity to transplanted islet cells. rejection still occurs and is a major limitation to islet transplantation.4 The induction of donor-specific transplantation across a species barrier. using bone marrow stem cells to produce chimerism. has been suggested as a potential approach to prevent rejection of transplanted cells and overcome the shortage of available grafts. We recently reported that acceptance of donorspecific islet cell xenografts was achieved in fully xenogeneic chimeras (WF rat to 810 mouse) when WF rat (RtlAU ) was the xenogeneic donor. To exclude a strain-specific effect. we have now evaluated whether similar tolerance would be present when F344 rat (RtiA 1) was used as the xenogeneic donor. We report here that long-term acceptance and function of donor-specific (F344 rat) xenogeneic pancreatic islet grafts could be achieved in fully xenogeneic chimeras (810 mouse + F344 rat to 810 mouse).