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人诱导多能干细胞衍生的心脏类器官对尾加压素II有反应:探索一种新型心脏药物测试模型。

Human iPSC-Derived cardiac organoids respond to urotensin II: Exploring a novel cardiac drug testing model.

作者信息

Wang Chu, Bai Rui, Jiang Huaizhi, Wu Fanghui, Liu Yanli, Yin Yifeng, Jia JianXin, Song Yunyang

机构信息

Department of Human Anatomy, Baotou Medical College, Inner Mongolia University of Science and Technology, Baotou, Inner Mongolia, 014040, China; State Key Laboratory of NBC Protection for Civilian, Beijing, 102205, China.

State Key Laboratory of NBC Protection for Civilian, Beijing, 102205, China; College of Life Science and Technology,Gansu Agricultural University, Lanzhou, Gansu, 730070, China.

出版信息

Biochem Biophys Res Commun. 2025 Aug 30;776:152140. doi: 10.1016/j.bbrc.2025.152140. Epub 2025 Jun 9.

DOI:10.1016/j.bbrc.2025.152140
PMID:40516442
Abstract

This study utilized human induced pluripotent stem cells to develop a self-assembled multicellular human cardiac organoid model comprising cardiomyocytes, endocardial and epicardial cells, cardiac fibroblasts, and atrial and ventricular myocytes. Capable of autonomous beating in vitro, this model closely mimics the characteristics of the native heart, demonstrating significant potential for drug testing and cardiotoxicity screening. The organoids' ability to simulate cellular communication reveals drug-induced cardiotoxicity induced by urotensin II, with dynamic molecular changes akin to those observed in heart disease patients, validating their utility in studying the pathophysiological mechanisms of heart disease. Although preliminary, these findings indicate that these organoids are sophisticated models offering deeper insights into the progression of heart disease and serving as a robust experimental platform for future therapeutic strategies.

摘要

本研究利用人类诱导多能干细胞构建了一种自组装的多细胞人类心脏类器官模型,该模型包含心肌细胞、心内膜和心外膜细胞、心脏成纤维细胞以及心房和心室肌细胞。该模型在体外能够自主跳动,紧密模拟了天然心脏的特征,在药物测试和心脏毒性筛查方面显示出巨大潜力。类器官模拟细胞通讯的能力揭示了由尾加压素 II 诱导的药物性心脏毒性,其动态分子变化类似于在心脏病患者中观察到的变化,证实了它们在研究心脏病病理生理机制方面的实用性。尽管这些发现尚属初步,但表明这些类器官是复杂的模型,能为深入了解心脏病进展提供见解,并作为未来治疗策略的强大实验平台。

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