Islet xenografts in fully xenogeneic (rat----mouse) chimeras: evidence for normal regulation of function in a xenogeneic mouse environment.

Abstract

BACKGROUND: Transplantation of untreated rat bone marrow into mouse recipients conditioned by total-body irradiation results in fully xenogeneic chimerism (rat----mouse). The chimerism is stable for up to 10 months, survival is excellent, and there is no evidence for graft-versus-host disease. We recently reported the long-term survival (greater than 180 days) of donor-specific pancreatic islet xenografts in these fully xenogeneic chimeras. METHODS: Chimeras were prepared and typed for chimerism at 6 weeks, and diabetes was induced by streptozocin injection. Donor-specific pancreatic islets were placed under the renal capsule and recipient blood glucose levels were followed biweekly. The aim of this study was to examine whether the transplanted pancreatic islets exhibited normal function in a xenogeneic environment and assess whether the islet xenografts were not only sufficient to support euglycemia but also regulated in function in response to a glucose challenge. RESULTS: We report for the first time that donor-specific rat islet xenografts were capable of producing normal basal and peak levels of insulin and responding to a glucose challenge in a manner similar to that of normal mouse islets. CONCLUSIONS: These data indicate that donor-specific rat islet xenografts are functional and regulated normally in fully xenogeneic (rat----mouse) chimeras