Preservation of pancreas in the University of Wisconsin solution supplemented with AP39 reduces reactive oxygen species production and improves islet graft function
Preservation of pancreas in the University of Wisconsin solution supplemented with AP39 reduces reactive oxygen species production and improves islet graft function
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DOI：
10.1111/ajt.16401
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发表时间：
2020-12-25
影响因子：
8.8
通讯作者：
Noguchi, Hirofumi
中科院分区：
文献类型：
--
作者：
Nishime, Kai;Miyagi-Shiohira, Chika;Noguchi, Hirofumi
缺血再灌注损伤（IRI）导致移植物功能延迟恢复和早期移植物丢失的发生率增加。最近有报道，硫化氢（H2S）保护器官移植物免受长期IRI。在这里，我们研究了在威斯康星州大学（UW）的解决方案补充了AP 39，这是一种针对H2S供体，保护胰岛对IRI和改善胰岛功能的胰腺保存。将猪胰腺保存在含有AP 39（UW + AP 39）或媒介物（UW）的UW溶液中18小时，随后分离胰岛。UW + AP 39组纯化前后的胰岛产量显著高于UW组。与从保存在载体中的胰腺分离的胰岛相比，从保存在UW + AP 39中的胰腺分离的胰岛表现出活性氧（ROS）产生水平显著降低和线粒体膜电位显著增加。我们发现，在UW + AP 39中保存的胰腺改善了链脲佐菌素诱导的糖尿病小鼠的胰岛移植的结果。这些结果表明，在UW + AP 39中保存胰腺保护胰岛移植物免受IRI，因此可以作为改善胰岛移植结果的新的临床策略。
Ischemia-reperfusion injury (IRI) results in increased rates of delayed graft function and early graft loss. It has recently been reported that hydrogen sulfide (H2S) protects organ grafts against prolonged IRI. Here, we investigated whether the preservation of pancreas in University of Wisconsin (UW) solution supplemented with AP39, which is a mitochondrial-targeted H2S donor, protected pancreatic islets against IRI and improved islet function. Porcine pancreata were preserved in the UW solution with AP39 (UW + AP39) or the vehicle (UW) for 18 h, followed by islet isolation. The islet yields before and after purification were significantly higher in the UW + AP39 group than in the UW group. The islets isolated from the pancreas preserved in UW + AP39 exhibited significantly decreased levels of reactive oxygen species (ROS) production and a significantly increased mitochondrial membrane potential as compared to the islets isolated from the pancreas preserved in the vehicle. We found that the pancreas preserved in UW + AP39 improved the outcome of islet transplantation in streptozotocin-induced diabetic mice. These results suggest that the preservation of pancreas in UW + AP39 protects the islet grafts against IRI and could thus serve as a novel clinical strategy for improving islet transplantation outcomes.