Three-dimensional filamentous human diseased cardiac tissue model.

Three-dimensional filamentous human diseased cardiac tissue model.
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DOI:
10.1016/j.biomaterials.2013.10.052
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发表时间:
2014-02
期刊:
影响因子:
14
通讯作者:
Healy, Kevin E.
Healy, Kevin E.
中科院分区:
工程技术1区
文献类型:
--
作者:
Ma, Zhen;Koo, Sangmo;Finnegan, Micaela A.;Loskill, Peter;Huebsch, Nathaniel;Marks, Natalie C.;Conklin, Bruce R.;Grigoropoulos, Costas P.;Healy, Kevin E.

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人类体外心脏组织模型将是理解、研究和开发治疗心律失常和相关心血管疾病的新策略的重大进展。我们开发了一种三维(3D)人心脏组织的体外模型,通过用来自健康野生型志愿者(WT)和患者特异性长QT综合征3型(LQT 3)诱导的多能干细胞(iPS-CM)的心肌细胞填充合成丝状基质来模拟浓缩和对齐的人心室肌。使用这种高度可控的心脏模型,我们研究了与LQT 3的电生理后果及其对一组药物的反应相关的收缩功能障碍。通过改变丝状基质的刚度,LQT 3 iPS-CM表现出不同水平的收缩性异常和对药物诱导的心脏毒性的易感性。
A human in vitro cardiac tissue model would be a significant advancement for understanding, studying, and developing new strategies for treating cardiac arrhythmias and related cardiovascular diseases. We developed an in vitro model of three-dimensional (3D) human cardiac tissue by populating synthetic filamentous matrices with cardiomyocytes derived from healthy wild-type volunteer (WT) and patient-specific long QT syndrome type 3 (LQT3) induced pluripotent stem cells (iPS-CMs) to mimic the condensed and aligned human ventricular myocardium. Using such a highly controllable cardiac model, we studied the contractility malfunctions associated with the electrophysiological consequences of LQT3 and their response to a panel of drugs. By varying the stiffness of filamentous matrices, LQT3 iPS-CMs exhibited different level of contractility abnormality and susceptibility to drug-induced cardiotoxicity.
基底硬度会影响离体成体心肌细胞的肌节和肋膜结构以及电生理功能。
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