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Three-dimensional filamentous human diseased cardiac tissue model
- Ma, Zhen, Koo, Sangmo, Finnegan, Micaela A., Loskill, Peter, Huebsch, Nathaniel, Marks, Natalie C., Conklin, Bruce R., Grigoropoulos, Costas P., Healy, Kevin E.
- Biomaterials 2014 v.35 no.5 pp. 1367-1377
- arrhythmia, cardiomyocytes, drugs, electrophysiology, humans, models, stem cells
- 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.