Generation of blood vessel organoids from human pluripotent stem cells
Generation of blood vessel organoids from human pluripotent stem cells
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DOI：
10.1038/s41596-019-0213-z
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发表时间：
2019-11-01
期刊：
影响因子：
14.8
通讯作者：
Penninger, Josef M.
中科院分区：
文献类型：
--
作者：
Wimmer, Reiner A.;Leopoldi, Alexandra;Penninger, Josef M.
血管是动物生命的基础，在许多疾病中起着关键作用，如中风、心肌梗死和糖尿病。血管系统由内皮细胞形成，内皮细胞排列在血管中并覆盖有壁细胞，特别是较小血管中的周细胞和较大直径血管中的血管平滑肌细胞（vSMC）。内皮细胞和壁细胞对于适当的血管功能都是必不可少的，并且可以来源于人多能干细胞（hPSC）。在这里，我们描述了一种从hPSC生成自组织3D人类血管类器官的方案，其表现出人类微血管的形态、功能和分子特征。这些类器官通过hPSC聚集体的中胚层诱导和随后在3D胶原I-基质胶基质中分化成内皮网络和周细胞来分化。血管在2-3周内形成，并且可以在可扩展的悬浮培养中进一步生长。重要的是，移植到免疫功能低下小鼠体内的体外分化的人类血管类器官可以进入小鼠循环，并指定为功能性动脉，小动脉和静脉。
Blood vessels are fundamental to animal life and have critical roles in many diseases, such as stroke, myocardial infarction and diabetes. The vasculature is formed by endothelial cells that line the vessel and are covered with mural cells, specifically pericytes in smaller vessels and vascular smooth muscle cells (vSMCs) in larger-diameter vessels. Both endothelial cells and mural cells are essential for proper blood vessel function and can be derived from human pluripotent stem cells (hPSCs). Here, we describe a protocol to generate self-organizing 3D human blood vessel organoids from hPSCs that exhibit morphological, functional and molecular features of human microvasculature. These organoids are differentiated via mesoderm induction of hPSC aggregates and subsequent differentiation into endothelial networks and pericytes in a 3D collagen I-Matrigel matrix. Blood vessels form within 2-3 weeks and can be further grown in scalable suspension culture. Importantly, in vitro-differentiated human blood vessel organoids transplanted into immunocompromised mice gain access to the mouse circulation and specify into functional arteries, arterioles and veins.