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最大限度减少小鼠肝内胰岛移植术后门静脉出血

Minimizing Post-Infusion Portal Vein Bleeding during Intrahepatic Islet Transplantation in Mice.

机构信息

Department of Surgery, Medical University of South Carolina.

Georgetown University;

出版信息

J Vis Exp. 2021 May 10(171). doi: 10.3791/62530.

DOI:10.3791/62530
PMID:34028442
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11094622/
Abstract

Although the liver is currently accepted as the primary transplantation site for human islets in clinical settings, islets are transplanted under the kidney capsule in most rodent preclinical islet transplantation studies. This model is commonly used because murine intrahepatic islet transplantation is technically challenging, and a high percentage of mice could die from surgical complications, especially bleeding from the injection site post-transplantation. In this study, two procedures that can minimize the incidence of post-infusion portal vein bleeding are demonstrated. The first method applies an absorbable hemostatic gelatin sponge to the injection site, and the second method involves penetrating the islet injection needle through the fat tissue first and then into the portal vein by using the fat tissue as a physical barrier to stop bleeding. Both methods could effectively prevent bleeding-induced mouse death. The whole liver section showing islet distribution and evidence of islet thrombosis post-transplantation, a typical feature for intrahepatic islet transplantation, were presented. These improved protocols refine the intrahepatic islet transplantation procedures and may help laboratories set up the procedure to study islet survival and function in pre-clinical settings.

摘要

尽管肝脏目前被认为是临床环境中人类胰岛移植的主要部位,但在大多数啮齿动物临床前胰岛移植研究中,胰岛是被移植到肾脏包膜下的。这种模型通常被使用,因为鼠类肝内胰岛移植技术上具有挑战性,而且很大比例的小鼠可能会因手术并发症而死亡,尤其是移植后注射部位出血。在这项研究中,展示了两种可以最小化输注后门静脉出血发生率的程序。第一种方法是将可吸收止血明胶海绵应用于注射部位,第二种方法是先用胰岛注射针穿透脂肪组织,然后将其作为物理屏障进入门静脉以阻止出血。这两种方法都可以有效地防止出血引起的小鼠死亡。还展示了整个肝段显示胰岛分布和移植后胰岛血栓形成的证据,这是肝内胰岛移植的一个典型特征。这些改进的方案完善了肝内胰岛移植程序,可能有助于实验室建立该程序以研究临床前环境中的胰岛存活和功能。

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本文引用的文献

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Alpha-1 antitrypsin suppresses macrophage activation and promotes islet graft survival after intrahepatic islet transplantation.α-1 抗胰蛋白酶抑制巨噬细胞活化并促进肝内胰岛移植后的胰岛移植物存活。
Am J Transplant. 2021 May;21(5):1713-1724. doi: 10.1111/ajt.16342. Epub 2020 Nov 16.
2
Intraportal Transplantation of Pancreatic Islets in Mouse Model.小鼠模型中胰岛的门静脉内移植
J Vis Exp. 2018 May 5(135):57559. doi: 10.3791/57559.
3
Purification of Hepatocytes and Sinusoidal Endothelial Cells from Mouse Liver Perfusion.从小鼠肝脏灌注中纯化肝细胞和肝窦内皮细胞。
J Vis Exp. 2018 Feb 12(132):56993. doi: 10.3791/56993.
4
Autologous Mesenchymal Stem Cell and Islet Cotransplantation: Safety and Efficacy.自体间充质干细胞与胰岛共移植:安全性和有效性。
Stem Cells Transl Med. 2018 Jan;7(1):11-19. doi: 10.1002/sctm.17-0139. Epub 2017 Nov 21.
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Effect of liver histopathology on islet cell engraftment in the model mimicking autologous islet cell transplantation.在模拟自体胰岛细胞移植的模型中肝脏组织病理学对胰岛细胞植入的影响。
Islets. 2017 Nov 2;9(6):140-149. doi: 10.1080/19382014.2017.1356558. Epub 2017 Sep 13.
6
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Diabetes. 2017 Apr;66(4):970-980. doi: 10.2337/db16-1036. Epub 2017 Jan 9.
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The state of the art of islet transplantation and cell therapy in type 1 diabetes.1型糖尿病胰岛移植与细胞治疗的现状
Acta Diabetol. 2016 Oct;53(5):683-91. doi: 10.1007/s00592-016-0847-z. Epub 2016 Feb 29.
8
Liposomal formulations of thrombomodulin increase engraftment after intraportal islet transplantation.血栓调节蛋白的脂质体制剂可增加门静脉内胰岛移植后的植入率。
Cell Transplant. 2010;19(11):1359-67. doi: 10.3727/096368910X513964. Epub 2010 Jun 29.
9
Thrombomodulin improves early outcomes after intraportal islet transplantation.血栓调节蛋白可改善门静脉内胰岛移植后的早期疗效。
Am J Transplant. 2009 Jun;9(6):1308-16. doi: 10.1111/j.1600-6143.2009.02652.x. Epub 2009 May 20.
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Intrahepatic islet transplant in the mouse: functional and morphological characterization.小鼠肝内胰岛移植:功能与形态学特征
Cell Transplant. 2008;17(12):1361-70. doi: 10.3727/096368908787648146.