Lakey J R, Warnock G L, Rajotte R V
Department of Surgery, University of Alberta, Edmonton, Canada.
Transplantation. 1996 Feb 15;61(3):506-8. doi: 10.1097/00007890-199602150-00033.
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.
本研究的目的是评估冷冻保存的胰岛在胸腺中的存活及功能，并确定少量同种异体胰岛是否能诱导对后续同种异体胰岛移植产生无反应状态。1500个新鲜分离的（n = 8）或2500个冻融的（n = 6）Wistar-Furth（RT1u/u）胰岛进行同基因移植，胸腺内移植后诱导长期正常血糖（两组中位生存时间[MST]均> 100天），而1500个冻融胰岛的同基因移植（n = 5）在恢复长期正常血糖方面并不一致。当1500个新鲜的（n = 6）或2500个冻融的（n = 6）Lewis（RT1l/l）胰岛与单次注射抗淋巴细胞血清联合移植时，可诱导长期正常血糖（两组MST均> 100天）。500个新鲜分离的Lewis胰岛胸腺内移植诱导了对第二次胸腺外同种异体移植的无反应状态（MST> 100天，n = 7）。然而，胸腺内移植500个（n = 10）或800个（n = 5）冷冻保存的Lewis胰岛并没有延长第二次胸腺外移植的存活时间（MST分别为19天和21天，与新鲜组相比P < 0.05，Mann-Whitney U检验）。这些结果表明，冷冻保存的胸腺内胰岛在胰岛数量增加时可使血糖正常化并维持正常血糖水平。观察到冷冻保存的胰岛在胸腺中存活时间延长；然而，少量冷冻保存的同种异体胰岛无法诱导对后续胸腺外胰岛移植产生无反应状态。
