title: 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.
authors.affiliation: Department of Surgery, University of Alberta, Edmonton, Canada.
authors.forename: J R
authors.initials: JR
authors.lastname: Lakey
authors.forename: G L
authors.initials: GL
authors.lastname: Warnock
authors.forename: R V
authors.initials: RV
authors.lastname: Rajotte
mesh_terms: D000818:Animals; D015925:Cryopreservation; D003921:Diabetes Mellitus, Experimental / Q000276:immunology / Q000601:surgery; D006085:Graft Survival; D007108:Immune Tolerance; D007165:Immunosuppression Therapy / Q000379:methods; D016381:Islets of Langerhans Transplantation / Q000276:immunology* / Q000379:methods; D051381:Rats; D011917:Rats, Inbred Lew; D011920:Rats, Inbred WF; D013950:Thymus Gland / Q000276:immunology; D016042:Transplantation, Heterotopic; D014184:Transplantation, Homologous; D014185:Transplantation, Isogeneic