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使用猪去细胞细胞外基质构建工程化 3D 胰岛微组织用于治疗糖尿病。

Construction of engineered 3D islet micro-tissue using porcine decellularized ECM for the treatment of diabetes.

机构信息

Department of Infectious Diseases, Third Xiangya Hospital, Central South University, Changsha, 410008, China.

College of Biology, Hunan University, Changsha, 410082, China.

出版信息

Biomater Sci. 2023 Aug 8;11(16):5517-5532. doi: 10.1039/d3bm00346a.

Abstract

Islet transplantation improves diabetes patients' long-term blood glucose control, but its success and utility are limited by cadaver availability, quality, and considerable islet loss after transplantation due to ischemia and inadequate angiogenesis. This study used adipose, pancreatic, and liver tissue decellularized extracellular matrix (dECM) hydrogels in an effort to recapitulate the islet sites inside the pancreas , and successfully generated viable and functional heterocellular islet micro-tissues using islet cells, human umbilical vein endothelial cells, and adipose-derived mesenchymal stem cells. The three-dimensional (3D) islet micro-tissues maintained prolonged viability and normal secretory function, and showed high drug sensitivity in drug testing. Meanwhile, the 3D islet micro-tissues significantly enhanced survival and graft function in a mouse model of diabetes. These supportive 3D physiomimetic dECM hydrogels can be used not only for islet micro-tissue culture , but also have great promise for islet transplantation for the treatment of diabetes.

摘要

胰岛移植可以改善糖尿病患者的长期血糖控制,但由于供体的可用性有限,以及移植后由于缺血和血管生成不足导致的胰岛大量损失,其成功率和实用性受到限制。本研究使用脂肪、胰腺和肝脏组织去细胞化细胞外基质(dECM)水凝胶,努力模拟胰岛在胰腺内的位置,并成功地使用胰岛细胞、人脐静脉内皮细胞和脂肪来源的间充质干细胞生成了有活力和功能的异细胞胰岛微组织。三维(3D)胰岛微组织保持了较长的活力和正常的分泌功能,并在药物测试中表现出高药物敏感性。同时,3D 胰岛微组织在糖尿病小鼠模型中显著提高了移植物的存活率和功能。这些支持性的 3D 生理性仿生 dECM 水凝胶不仅可用于胰岛微组织培养,而且在胰岛移植治疗糖尿病方面也具有很大的应用前景。

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