Three-dimensional filamentous human diseased cardiac tissue model

• Published in: Biomaterials Vol. 35; no. 5; pp. 1367 - 1377
• Main Authors: Ma, Zhen, Koo, Sangmo, Finnegan, Micaela A, Loskill, Peter, Huebsch, Nathaniel, Marks, Natalie C, Conklin, Bruce R, Grigoropoulos, Costas P, Healy, Kevin E
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.02.2014
• Subjects: Advanced Basic Science; Cardiac contractility; Cardiac disease model; Case-Control Studies; Cell Differentiation; Dentistry; Drug Evaluation, Preclinical; Drug testing; Flow Cytometry; Humans; Induced pluripotent stem cells; Induced Pluripotent Stem Cells - pathology; Long QT syndrome; Long QT Syndrome - drug therapy; Long QT Syndrome - pathology; Microscopy, Atomic Force; Microscopy, Electron, Scanning; Models, Biological; Real-Time Polymerase Chain Reaction; Two-photon initiated polymerization; Two-photon initiated polymerization; Long QT syndrome; Induced pluripotent stem cells; Cardiac disease model; Cardiac contractility; Drug testing
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2013.10.052

Abstract 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.