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Heart-on-a-chip using human iPSC-derived cardiomyocytes with an integrated vascular endothelial layer based on a culture patch as a potential platform for drug evaluation

诱导多能干细胞 人诱导多能干细胞 心脏毒性 生物医学工程 药品 人的心脏 图层(电子) 材料科学 医学 药理学 纳米技术 心脏病学 化学 内科学 化疗 胚胎干细胞 基因 生物化学
作者
Yadong Tang,Feng Tian,Xiaomin Miao,Dianqi Wu,Yaqi Wang,Han Wang,Kai You,Qinglan Li,Suqing Zhao,Wenlong Wang
出处
期刊:Biofabrication [IOP Publishing]
卷期号:15 (1): 015010-015010 被引量:17
标识
DOI:10.1088/1758-5090/ac975d
摘要

Abstract Many strategies have been adopted to construct in vitro myocardium models, which are of great value to both drug cardiotoxicity evaluation and cardiovascular drug development. In particular, the recent rapid development of human-induced pluripotent stem cell (hiPSC) technology and the rise of the organ-on-a-chip technique have provided great potential to achieve more physiologically relevant in vitro models. However, recapitulating the key role of the vasculature endothelial layer in drug action on myocardium in the models is still challenging. In this work, we developed an openable heart-on-a-chip system using highly purified functional hiPSC-derived cardiomyocytes (hiPSC-CMs) with an integrated vascular endothelial layer based on our previously proposed culture-patch method. The purity and functionality of the differentiated hiPSC-CMs were characterized, which were applied into the lower chamber of the sandwich-structured device to form the CM layer. The integrity and cell morphology of the endothelial layer on the culture patch as well as the influence of fluid shear force were studied, which was integrated in between the upper and lower chambers. The constructed heart-on-a-chip was finally applied for drug testing. The effect of two cardiac targeting drugs (isoproterenol and E-4031) directly on the hiPSC-CMs or after penetrating through the endothelial layer under static or dynamic conditions was evaluated. The results demonstrated the significance of a vascular layer in in vitro myocardium models for drug testing, as well as the advantage and potential of the proposed platform for cardiovascular drug evaluation with more human physiological relevance.
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