Human islet isolation and allotransplantation in 22 consecutive cases

This report provides our initial experience in islet isolation and intrahepatic allotransplantation in 21 patients. In group 1, 10 patients underwent combined liver-islet allotransplantation following upper-abdominal exenteration for cancer. In group 2, 4 patients received a combined liver-islet allograft for cirrhosis and diabetes. One patient had plasma C-peptide >3 pM and was therefore excluded from analysis. In group 3, 7 patients received 8 combined cadaveric kidney-islet grafts (one retransplant) for end-stage renal disease secondary to type 1 diabetes mellitus. The islets were separated by a modification of the automated method for human islet isolation and the preparations were infused into the portal vein. Immunosuppression was with FK506 (group 1) plus steroids (groups 2 and 3). Six patients in group 1 did not require insulin treatment for 5 to > 16 months. In groups 2 and 3 none of the patients became insulin-independent, although decreased insulin requirement and stabilization of diabetes were observed. Our results indicate that rejection is still a major factor limiting the clinical application of islet transplantation in patients with type 1 diabetes mellitus, although other factors such as steroid treatment may contribute to deteriorate islet engraftment and/or function. © 1992 by Williams and Wilkins

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

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

Augmentation of chimerism in whole organ recipients by simultaneous infusion of donor bone marrow cells

We had previously demonstrated the persistence of donor leukocytes in the peripheral blood and tissues of long-surviving kidneyl and live2-4 recipients who had stable graft function many years after transplantation.1-6 Donor cell chimerism has since been noted by other investigators in recipients of heart,7 liver,8 kidney,9 and lungl0 transplants. In an attempt to augment chimerism, and thereby facilitate graft function, we initiated a prospective trial to enhance this phenomenon by infusing 3 × l0(8)/kg unaltered donor bone marrow cells perioperatively into an unmodified recipient of whole organ from the same donor. Additionally, 53 recipients of whole organ alone were monitored as controls. Reported herein are the first 20 of 64 study patients and 33 of 53 control patients who are more than 120 days posttransplantation