Interventional strategies to prevent β-cell apoptosis in islet transplantation
Interventional strategies to prevent β-cell apoptosis in islet transplantation
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DOI：
10.2337/db05-1254
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发表时间：
2006-07-01
期刊：
影响因子：
7.7
通讯作者：
Shapiro, A. M. James
中科院分区：
文献类型：
--
作者：
Emamaullee, Juliet A.;Shapiro, A. M. James
相当大比例的移植的胰岛质量由于细胞凋亡导致的死亡而未能植入，并且已经探索了许多策略来抑制β细胞损失。抑制细胞凋亡的外部信号（即，cFLIP或A20）已经在实验性胰岛移植中进行了探索，但仅显示有限。冲击类似地，针对内在信号抑制的策略（即，BCL-2）尚未提供胰岛移植的实质性改善。最近，对阻断最终共同途径（即，X连锁凋亡抑制蛋白[XIAP]）在人类和啮齿动物移植模型中已显示出前景。此外，XIAP增强了小鼠胰岛移植物的长期存活。内在和外在的凋亡途径抑制的复杂性进行了深入讨论。
A substantial proportion of the transplanted islet mass fails to engraft due to death by apoptosis, and a number of strategies have been explored to inhibit beta-cell loss. Inhibition of extrinsic signals of apoptosis (i.e., cFLIP or A20) have been explored in experimental islet transplantation but have only shown limited. impact. Similarly, strategies targeted at intrinsic signal inhibition (i.e., BCL-2) have not yet provided substantial improvement in islet engraftment. Recently, investigation of downstream apoptosis inhibitors that block the final common pathway (i.e., X-linked inhibitor of apoptosis protein [XIAP]) have demonstrated promise in both human and rodent models of engraftment. In addition, XIAP has enhanced long-term murine islet allograft survival. The complexities of both intrinsic and extrinsic apoptotic pathway inhibition are discussed in depth.