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控制性循环死亡后供体胰腺的胰岛细胞产量降低,通过缩短无血预缺血时间和使用 IGL-1 冷藏液来预防。

Lower beta cell yield from donor pancreases after controlled circulatory death prevented by shortening acirculatory warm ischemia time and by using IGL-1 cold preservation solution.

机构信息

Diabetes Research Center, Vrije Universiteit Brussel (VUB), Brussels, Belgium.

Diabetes Clinic, Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussel), Brussels, Belgium.

出版信息

PLoS One. 2021 May 3;16(5):e0251055. doi: 10.1371/journal.pone.0251055. eCollection 2021.

Abstract

Organs from donors after controlled circulatory death (DCD III) exhibit a higher risk for graft dysfunction due to an initial period of warm ischemia. This procurement condition can also affect the yield of beta cells in islet isolates from donor pancreases, and hence their use for transplantation. The present study uses data collected and generated by our Beta Cell Bank to compare the number of beta cells in isolates from DCD III (n = 141) with that from donors after brain death (DBD, n = 609), before and after culture, and examines the influence of donor and procurement variables. Beta cell number per DCD III-organ was significantly lower (58 x 106 versus 84 x 106 beta cells per DBD-organ; p < 0.001) but their purity (24% insulin positive cells) and insulin content (17 μg / 106 beta cells in DCD III-organs versus 19 μg / 106 beta cells in DBD-organs) were similar. Beta cell number correlated negatively with duration of acirculatory warm ischemia time above 10 min; for shorter acirculatory warm ischemia time, DCD III-organs did not exhibit a lower beta cell yield (74 x 106 beta cells). Use of Institut Georges Lopez-1 cold preservation solution instead of University of Wisconsin solution or histidine-tryptophan-ketoglutarate also protected against the loss in beta cell yield from DCD III-organs (86 x 106 for IGL-1 versus 54 x 106 and 65 x 106 beta cells respectively, p = 0.042). Multivariate analysis indicates that both limitation of acirculatory warm ischemia time and use of IGL-1 prevent the reduced beta cell yield in islet cell isolates from DCD III-organs.

摘要

来自控制性循环死亡(DCD III)供体的器官由于初始的热缺血期而表现出更高的移植物功能障碍风险。这种采集条件还会影响胰岛分离物中β细胞的产量,从而影响其用于移植。本研究使用我们的β细胞库收集和生成的数据,比较了 DCD III(n = 141)和脑死亡(DBD,n = 609)供体的胰岛分离物中的β细胞数量,分别在培养前后,并检查了供体和采集变量的影响。每个 DCD III 器官的β细胞数量明显较低(58 x 106 与每个 DBD 器官的 84 x 106 β细胞;p < 0.001),但其纯度(24%胰岛素阳性细胞)和胰岛素含量(DCD III 器官中的 17 μg / 106 β细胞与 DBD 器官中的 19 μg / 106 β细胞)相似。β细胞数量与循环性热缺血时间超过 10 分钟的时间呈负相关;对于较短的循环性热缺血时间,DCD III 器官不会表现出较低的β细胞产量(74 x 106 β细胞)。使用 Institut Georges Lopez-1 冷保存溶液而不是威斯康星大学溶液或组氨酸-色氨酸-酮戊二酸也可以防止 DCD III 器官的β细胞产量损失(IGL-1 为 86 x 106 ,分别为 54 x 106 和 65 x 106 β细胞,p = 0.042)。多变量分析表明,循环性热缺血时间的限制和 IGL-1 的使用都可以防止 DCD III 器官的胰岛分离物中β细胞产量减少。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6208/8092795/be98b7556058/pone.0251055.g001.jpg

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