Tricultured Cell Sheets Develop into Functional Pancreatic Islet Tissue with a Vascular Network
Tricultured Cell Sheets Develop into Functional Pancreatic Islet Tissue with a Vascular Network
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DOI：
10.1089/ten.tea.2022.0167
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发表时间：
2023-01-27
影响因子：
4.1
通讯作者：
Shimizu, Tatsuya
中科院分区：
文献类型：
--
作者：
Homma, Jun;Sekine, Hidekazu;Shimizu, Tatsuya
影响声明本研究评估了含有胰岛β细胞、血管内皮细胞和间充质干细胞的培养细胞片是否能够形成胰岛组织。有两个主要发现。首先，在体外培养的细胞片中的胰岛β细胞自组织成被致密血管网络包围的胰岛结构。第二，三层培养的薄片很好地嫁接到大鼠肌肉上，并发育成具有丰富血管的胰岛素分泌组织。培养的细胞片可以用作药物测试的假胰岛模型，并且可能具有发展成可移植物的潜力，用于临床应用。然而，胰岛β细胞在缺氧条件下易发生凋亡，因此用于移植β细胞的技术必须保持细胞在体内的活力。本研究描述了一个三培养细胞片的发展，这是通过共培养胰岛β细胞，血管内皮细胞，和间充质干细胞1天。在体外培养的细胞片中，胰岛β细胞自组织成胰岛样结构，周围有密集的血管网。三层培养的细胞片在体内移植后移植良好，并发育成具有丰富血管和高密度胰岛β细胞的胰岛素分泌组织。我们预计，培养的细胞片可用作药物测试的体外假胰岛模型，并可能有潜力发展成用于再生医学的可移植物。
Impact statementThis research assessed whether tricultured cell sheets containing islet beta-cells, vascular endothelial cells, and mesenchymal stem cells were able to form islet tissue. There were two main findings. First, the islet beta-cells in the tricultured cell sheet self-organized into islet structures surrounded by a dense vascular network in vitro. Second, triple-layered tricultured sheets engrafted well onto rat muscle and developed into insulin-secreting tissue with an abundance of blood vessels. The tricultured cell sheet could be used as a pseudo-islet model for pharmaceutical testing and may have potential for development into a transplantable graft for application in the clinical setting.Methods to induce islet beta-cells from induced pluripotent stem cells or embryonic stem cells have been established. However, islet beta-cells are susceptible to apoptosis under hypoxic conditions, so the technique used to transplant beta-cells must maintain the viability of cells in vivo. This study describes the development of a tricultured cell sheet, which was made by coculturing islet beta-cells, vascular endothelial cells, and mesenchymal stem cells for 1 day. The islet beta-cells in the tricultured cell sheet self-organized into islet-like structures surrounded by a dense vascular network in vitro. Triple-layered tricultured cell sheets engrafted well after transplantation in vivo and developed into insulin-secreting tissue with abundant blood vessels and a high density of islet beta-cells. We anticipate that the tricultured cell sheet could be used as an in vitro pseudo-islet model for pharmaceutical testing and may have potential for development into transplantable grafts for use in regenerative medicine.