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Engineered 3D vessel-on-chip using hiPSC-derived endothelial- and vascular smooth muscle cells
Stem Cell Reports ( IF 5.9 ) Pub Date : 2021-09-02 , DOI: 10.1016/j.stemcr.2021.08.003
Marc Vila Cuenca 1 , Amy Cochrane 2 , Francijna E van den Hil 2 , Antoine A F de Vries 3 , Saskia A J Lesnik Oberstein 4 , Christine L Mummery 2 , Valeria V Orlova 2
Affiliation  

Crosstalk between endothelial cells (ECs) and pericytes or vascular smooth muscle cells (VSMCs) is essential for the proper functioning of blood vessels. This balance is disrupted in several vascular diseases but there are few experimental models which recapitulate this vascular cell dialogue in humans. Here, we developed a robust multi-cell type 3D vessel-on-chip (VoC) model based entirely on human induced pluripotent stem cells (hiPSCs). Within a fibrin hydrogel microenvironment, the hiPSC-derived vascular cells self-organized to form stable microvascular networks reproducibly, in which the vessels were lumenized and functional, responding as expected to vasoactive stimulation. Vascular organization and intracellular Ca2+ release kinetics in VSMCs could be quantified using automated image analysis based on open-source software CellProfiler and ImageJ on widefield or confocal images, setting the stage for use of the platform to study vascular (patho)physiology and therapy.



中文翻译:

使用 hiPSC 衍生的内皮和血管平滑肌细胞设计的 3D 血管芯片

内皮细胞 (EC) 和周细胞或血管平滑肌细胞 (VSMC) 之间的串扰对于血管的正常功能至关重要。这种平衡在几种血管疾病中被破坏,但很少有实验模型能够概括人类的这种血管细胞对话。在这里,我们开发了一种完全基于人类诱导多能干细胞 (hiPSC) 的强大的多细胞型 3D 血管芯片 (VoC) 模型。在纤维蛋白水凝胶微环境中,hiPSC 衍生的血管细胞自组织以可重复地形成稳定的微血管网络,其中血管具有管腔和功能,对血管活性刺激作出预期反应。血管组织和细胞内 Ca 2+VSMC 中的释放动力学可以使用基于开源软件 CellProfiler 和 ImageJ 的宽场或共聚焦图像上的自动图像分析进行量化,为使用该平台研究血管(病理)生理学和治疗奠定了基础。

更新日期:2021-09-14
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