A Novel Device for Islet Transplantation Providing Immune Protection and Oxygen Supply
A Novel Device for Islet Transplantation Providing Immune Protection and Oxygen Supply
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DOI：
10.1055/s-0030-1267916
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发表时间：
2010-12-01
影响因子：
2.2
通讯作者：
Barkai, U.
中科院分区：
文献类型：
--
作者：
Ludwig, B.;Zimerman, B.;Barkai, U.
胰岛移植作为一种生物β细胞替代疗法已成为实现1型糖尿病患者代谢控制恢复的有希望的选择。然而，胰岛移植物功能的部分或完全丧失发生在移植后相对较短的时间内（数月至数年）。早期移植功能障碍的高发率归因于胰岛存活率和/或功能低下，并由血管内（肝）移植部位的先天炎症反应和胰岛植入前初始营养/氧气供应的严重缺乏介导。此外，强制性免疫抑制剂的致糖尿病作用、同种异体免疫控制的限制以及自身免疫的复发限制了胰岛移植的长期成功。为了消除即时血液介导的炎症反应并为胰岛移植物提供氧气供应，我们开发了一种血管外（皮下）移植大腔（“beta Air”装置）。该装置将胰岛固定在海藻酸盐中，通过浸渍海藻酸盐的薄亲水聚四氟乙烯膜保护胰岛免受免疫系统的影响，并通过每天用氧气- co(2)混合物补充氧气。我们已经成功地证明了在健康的小型猪同种异体皮下移植后，充氧大腔室在维持胰岛活力和功能以及免疫保护方面的应用。考虑到目前门静脉内胰岛移植的局限性和胰岛移植的适应症主要是由于必要的免疫抑制治疗，这项工作很可能会导致手术的显着改进，并为猪胰岛细胞异种移植开辟进一步的策略。
Islet transplantation as a biological beta-cell replacement therapy has emerged as a promising option for achieving restoration of metabolic control in type 1 diabetes patients. However, partial or complete loss of islet graft function occurs in relatively short time (months to few years) after implantation. The high rate of early transplant dysfunction has been attributed to poorly viable and/or functional islets and is mediated by innate inflammatory response at the intravascular (hepatic) transplant site and critical lack of initial nutrient/oxygen supply prior to islet engraftment. In addition, the diabetogenic effect of mandatory immunosuppressive agents, limited control of alloimmunity, and the recurrence of autoimmunity limit the long-term success of islet transplantation. In order to abrogate instant blood-mediated inflammatory reaction and to provide oxygen supply for the islet graft, we have developed an extravascular (subcutaneous) transplant macrochamber (the 'beta Air' device). This device contains islets immobilized in alginate, protected from the immune system by a thin hydrophilized teflon membrane impregnated with alginate and supplied with oxygen by daily refueling with oxygen-CO(2) mixture. We have demonstrated successful utilization of the oxygen-refueling macrochamber for sustained islet viability and function as well as immunoprotection after allogeneic subcutaneous transplantation in healthy minipigs. Considering the current limitations of intraportal islet engraftment and the restricted indication for islet transplantation mainly due to necessary immunosuppressive therapy, this work could very likely lead to remarkable improvements in the procedure and moreover opens up further strategies for porcine islet cell xenotransplantation.