Three-dimensional filamentous human diseased cardiac tissue model

Biomaterials. 2014 Feb;35(5):1367-77. doi: 10.1016/j.biomaterials.2013.10.052. Epub 2013 Nov 21.


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.

Keywords: Cardiac contractility; Cardiac disease model; Drug testing; Induced pluripotent stem cells; Long QT syndrome; Two-photon initiated polymerization.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Case-Control Studies
  • Cell Differentiation
  • Drug Evaluation, Preclinical
  • Flow Cytometry
  • Humans
  • Induced Pluripotent Stem Cells / pathology
  • Long QT Syndrome / drug therapy
  • Long QT Syndrome / pathology*
  • Microscopy, Atomic Force
  • Microscopy, Electron, Scanning
  • Models, Biological*
  • Real-Time Polymerase Chain Reaction