The pancreatic islet is a highly vascularized micro-organ, and rapid revascularization postislet transplantation is important for islet survival and function. However, the various mechanisms involved in islet revascularization are not fully understood, and we currently lack good in vitro platforms to explore this. Our aim for this study was to generate perfusable microvascular networks in a microfluidic chip device, in which islets could be easily integrated, to establish an in vitro platform for investigations on islet–microvasculature interactions. We compared the ability of mesenchymal stem cells (MSCs) and fibroblasts to support microvascular network formation by human umbilical vein endothelial cells (HUVECs) and human induced pluripotent stem cell-derived endothelial colony-forming cell in two-dimensional and three-dimensional models of angiogenesis, and tested the effect of different culture media on microvessel formation. HUVECs that were supported by MSCs formed patent and perfusable networks in a fibrin gel, whereas networks supported by fibroblasts rapidly regressed. Network morphology could be controlled by adjusting relative cell numbers and densities. Incorporation of isolated rat islets demonstrated that islets recruit local microvasculature in vitro, but that the microvessels did not invade islets, at least during the course of these studies. This in vitro microvascularization platform can provide a useful tool to study how various parameters affect islet integration with microvascular networks and could also be utilized for studies of vascularization of other organ systems.

中文翻译：

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三维芯片培养中微血管网络的形成及其与胰岛的相互作用。


胰岛是一种高度血管化的微器官，胰岛移植后的快速血运重建对于胰岛的存活和功能非常重要。然而，胰岛血运重建涉及的各种机制尚不完全清楚，我们目前缺乏良好的体外平台来探索这一点。我们这项研究的目的是在微流控芯片装置中生成可灌注的微血管网络，其中胰岛可以轻松集成，以建立用于研究胰岛-微血管相互作用的体外平台。我们在二维和三维模型中比较了间充质干细胞（MSC）和成纤维细胞支持人脐静脉内皮细胞（HUVEC）和人诱导多能干细胞衍生的内皮集落形成细胞形成微血管网络的能力。血管生成，并测试不同培养基对微血管形成的影响。由间充质干细胞支持的 HUVEC 在纤维蛋白凝胶中形成专利和可灌注网络，而由成纤维细胞支持的网络迅速退化。网络形态可以通过调整相对细胞数量和密度来控制。分离的大鼠胰岛的掺入表明，胰岛在体外募集局部微血管，但微血管没有侵入胰岛，至少在这些研究过程中是这样。该体外微血管化平台可以提供有用的工具来研究各种参数如何影响胰岛与微血管网络的整合，也可用于其他器官系统血管化的研究。