Three-dimensional filamentous human diseased cardiac tissue model

  • Zhen Ma
  • , Sangmo Koo
  • , Micaela A. Finnegan
  • , Peter Loskill
  • , Nathaniel Huebsch
  • , Natalie C. Marks
  • , Bruce R. Conklin
  • , Costas P. Grigoropoulos
  • , Kevin E. Healy

Research output: Contribution to journalArticlepeer-review

111 Scopus citations

Abstract

A human invitro 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 invitro 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.

Original languageEnglish
Pages (from-to)1367-1377
Number of pages11
JournalBiomaterials
Volume35
Issue number5
DOIs
StatePublished - Feb 2014

Keywords

  • Cardiac contractility
  • Cardiac disease model
  • Drug testing
  • Induced pluripotent stem cells
  • Long QT syndrome
  • Two-photon initiated polymerization

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