The effective deployment of arterial (AECs), venous (VECs) and stem cell-derived endothelial cells (PSC-ECs) in clinical applications requires understanding of their distinctive phenotypic and functional characteristics, including their responses to microenvironmental cues. Efforts to mimic the in-vivo vascular basement membrane milieu have led to the design and fabrication of nano- and micro-topographical substrates. Although the basement membrane architectures of arteries and veins are different, investigations into the effects of substrate topographies have so far focused on generic EC characteristics. Thus, topographical modulation of arterial- or venous-specific EC phenotype and function remains unknown. Here, we comprehensively evaluated the effects of 16 unique topographies on primary AECs, VECs and human PSC-ECs using a Multi Architectural (MARC) Chip. Gratings and micro-lenses augmented venous-specific phenotypes and depressed arterial functions in VECs; while AECs did not respond consistently to topography. PSC-ECs exhibited phenotypic and functional maturation towards an arterial subtype with increased angiogenic potential, NOTCH1 and Ac-LDL expression on gratings. Specific topographies could elicit different phenotypic and functional changes, despite similar morphological response in different ECs, demonstrating no direct correlation between the two responses.

中文翻译：

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地形在人类原代和干细胞来源的内皮细胞中引起不同的表型和功能。

在临床应用中有效部署动脉（AEC），静脉（VEC）和干细胞衍生的内皮细胞（PSC-EC）需要了解其独特的表型和功能特征，包括它们对微环境线索的反应。模仿体内血管基底膜环境的努力导致了纳米和微形底物的设计和制造。尽管动脉和静脉的基底膜结构不同，但迄今为止，对基底形貌影响的研究主要集中在通用EC特性上。因此，动脉或静脉特异性EC表型和功能的地形调制仍然是未知的。在这里，我们综合评估了16种独特地形对主要AEC的影响，使用多架构（MARC）芯片的VEC和人类PSC-EC。光栅和微透镜增强了VECs的静脉特异性表型和动脉功能低下；而AEC对地形的反应不一致。PSC-EC表现出朝向动脉亚型的表型和功能成熟，在血管上具有增加的血管生成潜能，NOTCH1和Ac-LDL表达。尽管在不同的EC中有相似的形态学反应，但特定的地形图可能会引发不同的表型和功能变化，这表明这两种反应之间没有直接相关性。PSC-EC表现出朝向动脉亚型的表型和功能成熟，在血管上具有增加的血管生成潜能，NOTCH1和Ac-LDL表达。尽管在不同的EC中有相似的形态反应，但特定的地形图可能会引发不同的表型和功能变化，这表明这两种反应之间没有直接相关性。PSC-EC表现出朝向动脉亚型的表型和功能成熟，在血管上具有增加的血管生成潜能，NOTCH1和Ac-LDL表达。尽管在不同的EC中有相似的形态学反应，但特定的地形图可能会引发不同的表型和功能变化，这表明这两种反应之间没有直接相关性。