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 journalArticle

67 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 (US)
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

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

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  • Cite this

    Ma, Z., Koo, S., Finnegan, M. A., Loskill, P., Huebsch, N., Marks, N. C., Conklin, B. R., Grigoropoulos, C. P., & Healy, K. E. (2014). Three-dimensional filamentous human diseased cardiac tissue model. Biomaterials, 35(5), 1367-1377. https://doi.org/10.1016/j.biomaterials.2013.10.052