心力衰竭
纤维化
心脏纤维化
转录组
诱导多能干细胞
心脏病学
生物医学工程
癌症研究
医学
生物
内科学
基因表达
基因
生物化学
胚胎干细胞
作者
Olya Mastikhina,Byeong-Ui Moon,Karen Williams,Rupal Hatkar,Dakota Gustafson,Omar Mourad,Xuetao Sun,Margaret Koo,Alan Y.L. Lam,Yu Sun,Jason E. Fish,Elton T. Young,Sara S. Nunes
出处
期刊:Biomaterials
[Elsevier]
日期:2020-03-01
卷期号:233: 119741-119741
被引量:111
标识
DOI:10.1016/j.biomaterials.2019.119741
摘要
While interstitial fibrosis plays a significant role in heart failure, our understanding of disease progression in humans is limited. To address this limitation, we have engineered a cardiac-fibrosis-on-a-chip model consisting of a microfabricated device with live force measurement capabilities using co-cultured human cardiac fibroblasts and pluripotent stem cell-derived cardiomyocytes. Transforming growth factor-β was used as a trigger for fibrosis. Here, we have reproduced the classic hallmarks of fibrosis-induced heart failure including high collagen deposition, increased tissue stiffness, BNP secretion, and passive tension. Force of contraction was significantly decreased in fibrotic tissues that displayed a transcriptomic signature consistent with human cardiac fibrosis/heart failure. Treatment with an anti-fibrotic drug decreased tissue stiffness and BNP secretion, with corresponding changes in the transcriptomic signature. This model represents an accessible approach to study human heart failure in vitro, and allows for testing anti-fibrotic drugs while facilitating the real-time assessment of cardiomyocyte function.
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