Clinical Islet Transplant Program, University of Alberta, Edmonton, AB, Canada.
Transplantation. 2010 Feb 15;89(3):361-5. doi: 10.1097/TP.0b013e3181bcdbe8.
The ability of supplemental islet infusions (SII) to restore insulin independence in islet transplant recipients with graft dysfunction has been attributed to the coadministration of exenatide. However, improving islet transplant outcomes could explain the success of SII. We aimed to determine the effect on islet graft function and insulin independence of SII using these new protocols, without the use of exenatide.
Seventeen islet transplant recipients underwent SIIs after developing graft dysfunction requiring insulin use. For induction therapy, four subjects received daclizumab induction therapy, whereas 13 subjects received thymoglobulin and etanercept. Maintenance immunosuppression consisted of sirolimus+tacrolimus or tacrolimus+cellcept.
SII was performed 49.3+/-4.8 months (mean+/-SEM) after the preceding islet transplant. Subjects received significantly lower islet mass with their SII compared with initial transplant(s) (6076+/-492 vs. 9071+/-796 IEQ/kg; P=0.003). Fifteen of the 17 subjects (88.2%) became insulin independent 2.4+/-0.5 months after SII. Insulin-independent duration after SII exceeded that of the initial transplant(s) (24.8+/-2.2 vs. 14.2+/-2.6 months by Kaplan-Meier analysis, P=0.009). Subjects show improved glycemic control after SII (HbA1c 7.0%+/-0.2% pre-SII vs. 6.1%+/-0.2% post-SII, P=0.005) and did not become immunosensitized.
Using current protocols, SII in the absence of exenatide results in impressive insulin-independence rates and the durability of insulin independence seems to be promising. However, a beneficial effect of exenatide should not be discounted until tested in randomized controlled studies.
补充胰岛输注（SII）能够恢复胰岛移植受者移植物功能障碍时的胰岛素独立性，这归因于外泌体的共同给药。然而，改善胰岛移植的结果可以解释 SII 的成功。我们旨在确定使用这些新方案的 SII 对胰岛移植物功能和胰岛素独立性的影响，而不使用外泌体。
17 名胰岛移植受者在需要使用胰岛素的移植物功能障碍后接受 SII。诱导治疗中，4 名患者接受达珠单抗诱导治疗，而 13 名患者接受胸腺球蛋白和依那西普。维持免疫抑制包括西罗莫司+他克莫司或他克莫司+细胞素。
SII 是在前一次胰岛移植后 49.3+/-4.8 个月（平均值+/-SEM）进行的。与初始移植相比，患者在 SII 中接受的胰岛质量明显较低（6076+/-492 与 9071+/-796 IEQ/kg；P=0.003）。17 名患者中的 15 名（88.2%）在 SII 后 2.4+/-0.5 个月实现了胰岛素独立性。SII 后的胰岛素独立性持续时间超过初始移植（Kaplan-Meier 分析为 24.8+/-2.2 与 14.2+/-2.6 个月，P=0.009）。患者在 SII 后血糖控制得到改善（SII 前 HbA1c 为 7.0%+/-0.2%，SII 后为 6.1%+/-0.2%，P=0.005），且未发生免疫致敏。
在没有外泌体的情况下，使用当前方案进行 SII 可实现令人印象深刻的胰岛素独立性率，并且胰岛素独立性的持久性似乎很有前景。然而，在随机对照研究中测试之前，不应排除外泌体的有益作用。
