Pancreas Preservation with a Neutrophil Elastase Inhibitor, Alvelestat, Contributes to Improvement of Porcine Islet Isolation and Transplantation.
Pancreas Preservation with a Neutrophil Elastase Inhibitor, Alvelestat, Contributes to Improvement of Porcine Islet Isolation and Transplantation.
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中性粒细胞弹性酶抑制剂Alvelestat保存胰腺有助于改善猪胰岛的分离和移植。
DOI：
10.3390/jcm11154290
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发表时间：
2022-07-23
影响因子：
3.9
通讯作者：
Noguchi, Hirofumi
中科院分区：
文献类型：
--
作者：
Otsuka, Ryusei;Miyagi-Shiohira, Chika;Kuwae, Kazuho;Nishime, Kai;Tamaki, Yoshihito;Yonaha, Tasuku;Sakai-Yonaha, Mayuko;Yamasaki, Ikuo;Shinzato, Misaki;Saitoh, Issei;Watanabe, Masami;Noguchi, Hirofumi
对于胰岛移植，胰腺的获取、保存和胰岛分离破坏细胞和非细胞成分，并激活诸如驻留中性粒细胞的成分，其在胰岛存活受损中起重要作用。中性粒细胞弹性蛋白酶（NE）抑制剂如西维来司和α1-抗胰蛋白酶可促进胰岛分离和移植。在这项研究中，我们调查了是否与alvelestat，一种新的NE抑制剂，胰腺保存，提高猪胰岛产量和功能。将猪胰腺用或不用5 μM alvelestat保存18 h，并进行胰岛分离。纯化前和纯化后的胰岛产量在alvelestat（+）组中显著高于alvelestat（-）组。将胰岛移植到链脲佐菌素诱导的糖尿病小鼠中后，alvelestat（+）和alvelestat（-）组中分别有55%和5%的糖尿病小鼠的血糖水平达到正常血糖范围。这些结果表明，用alvelestat保存胰腺可提高胰岛产量和移植物功能，因此可作为改善胰岛移植结局的新临床策略。
For pancreatic islet transplantation, pancreas procurement, preservation, and islet isolation destroy cellular and non-cellular components and activate components such as resident neutrophils, which play an important role in the impairment of islet survival. It has been reported that inhibitors of neutrophil elastase (NE), such as sivelestat and α1-antitrypsin, could contribute to improvement of islet isolation and transplantation. In this study, we investigated whether pancreatic preservation with alvelestat, a novel NE inhibitor, improves porcine islet yield and function. Porcine pancreata were preserved with or without 5 μM alvelestat for 18 h, and islet isolation was performed. The islet yields before and after purification were significantly higher in the alvelestat (+) group than in the alvelestat (−) group. After islet transplantation into streptozotocin-induced diabetic mice, blood glucose levels reached the normoglycemic range in 55% and 5% of diabetic mice in the alvelestat (+) and alvelestat (−) groups, respectively. These results suggest that pancreas preservation with alvelestat improves islet yield and graft function and could thus serve as a novel clinical strategy for improving the outcome of islet transplantation.
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影响因子：
6.2
作者：
Ito, Tathei;Omori, Keiko;Mullen, Yoko
通讯作者：
Mullen, Yoko
影响因子：
4.3
作者：
Kono, Tomoharu;Okada, Shin-ichi;Saito, Motoaki
通讯作者：
Saito, Motoaki
DOI：
10.1073/pnas.0505579102
发表时间：
2005-08-23
影响因子：
11.1
作者：
Lewis, EC;Shapiro, L;Dinarello, CA
通讯作者：
Dinarello, CA
影响因子：
8.8
作者：
Noguchi, H.;Iwanaga, Y.;Matsumoto, S.
通讯作者：
Matsumoto, S.
影响因子：
16.2
作者：
Foster, Eric D.;Bridges, Nancy D.;Alejandro, Rodolfo
通讯作者：
Alejandro, Rodolfo