Intrathymic transplantation of fresh and cryopreserved islets for the induction of a state of unresponsiveness in rats.

Abstract

The aim of this study was to assess the survival and function of cryopreserved islets in the thymus and to determine whether small numbers of allogeneic islets could induce a state of unresponsiveness to subsequent allogeneic islet grafts. Isografts of 1500 freshly isolated (n = 8) or 2500 frozen-thawed (n = 6) Wistar-Furth (RT1u/u) islets induced long-term normoglycemia after intrathymic transplantation (median survival time [MST] > 100 days in both groups), whereas isografts of 1500 frozen-thawed islets (n = 5) were inconsistent in restoring long-term normoglycemia. Transplantation of 1500 fresh (n = 6) or 2500 frozen-thawed (n = 6) Lewis (RT1l/l) islets induced long-term normoglycemia (MST > 100 days in both groups) when islets were transplanted in conjunction with a single injection of antilymphocyte serum. Intrathymic transplants of 500 freshly isolated Lewis islets induced a state of unresponsiveness to a second extrathymic allotransplant (MST > 100 days, n = 7). However, transplantation of 500 (n = 10) or 800 (n = 5) cryopreserved Lewis islets intrathymically did not prolong survival of a second extrathymic transplant (MST 19 and 21 days, P < 0.05 vs. fresh group, Mann-Whitney U test). These results demonstrate that cryopreserved intrathymic islets can normalize and maintain euglycemia providing the islet mass is augmented. Prolonged survival of cryopreserved islets in the thymus was observed; however, small numbers of allogeneic cryopreserved islets were unable to induced a state of unresponsiveness to a subsequent extrathymic islet graft.