A Novel Three-Dimensional Human Peritubular Microvascular System
A Novel Three-Dimensional Human Peritubular Microvascular System
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DOI：
10.1681/asn.2015070747
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发表时间：
2016-08-01
影响因子：
13.6
通讯作者：
Zheng, Ying
中科院分区：
文献类型：
--
作者：
Ligresti, Giovanni;Nagao, Ryan J.;Zheng, Ying
人肾管周毛细血管特别容易受到损伤，导致血管生成失调、毛细血管稀疏和退化，以及肾功能进行性丧失。然而，人们对人类肾脏微血管的结构和功能知之甚少。在这里，我们分离、纯化和表征了人肾管周微血管内皮细胞（HKMEC），并在流动导向的微生理系统中重建了三维人肾微血管系统。通过将上皮细胞去除和在含有高浓度血管内皮生长因子的培养基中进行细胞培养相结合，我们获得了大量高纯度的 HKMEC。与其他内皮细胞不同，分离的 HKMEC 依赖于高血管内皮生长因子浓度来生存和生长，并表现出高管状生成但低血管生成潜力。此外，HKMEC 具有不同的转录谱。在流动下，HKMEC 形成薄薄的有孔内皮，具有功能性渗透屏障。总之，这个三维HKMEC特异性微生理系统再现了人肾微血管的结构和功能，并表现出与其他微血管内皮细胞不同的表型特征。
Human kidney peritubular capillaries are particularly susceptible to injury, resulting in dysregulated angiogenesis, capillary rarefaction and regression, and progressive loss of kidney function. However, little is known about the structure and function of human kidney microvasculature. Here, we isolated, purified, and characterized human kidney peritubular microvascular endothelial cells (HKMECs) and reconstituted a three-dimensional human kidney microvasculature in a flow-directed microphysiologic system. By combining epithelial cell depletion and cell culture in media with high concentrations of vascular endothelial growth factor, we obtained HKMECs of high purity in large quantity. Unlike other endothelial cells, isolated HKMECs depended on high vascular endothelial growth factor concentration for survival and growth and exhibited high tubulogenic but low angiogenic potential. Furthermore, HKMECs had a different transcriptional profile. Under flow, HKMECs formed a thin fenestrated endothelium with a functional permeability barrier. In conclusion, this three-dimensional-HKMEC-specific-microphysiologic system recapitulates human kidney microvascular structure and function and shows phenotypic characteristics different from those of other microvascular endothelial cells.