诱导多能干细胞
类有机物
基质凝胶
壁细胞
细胞生物学
生物
血管生成
胚胎干细胞
中胚层
干细胞
解剖
血管
内皮干细胞
祖细胞
血管生成
体外
癌症研究
内分泌学
基因
生物化学
作者
Reiner Wimmer,Alexandra Leopoldi,Martin Aichinger,Dontscho Kerjaschki,Josef Penninger
出处
期刊:Nature Protocols
[Springer Nature]
日期:2019-09-25
卷期号:14 (11): 3082-3100
被引量:176
标识
DOI:10.1038/s41596-019-0213-z
摘要
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.
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