A Platform for Generation of Chamber-Specific Cardiac Tissues and Disease Modeling

Cell. 2019 Feb 7;176(4):913-927.e18. doi: 10.1016/j.cell.2018.11.042. Epub 2019 Jan 24.


Tissue engineering using cardiomyocytes derived from human pluripotent stem cells holds a promise to revolutionize drug discovery, but only if limitations related to cardiac chamber specification and platform versatility can be overcome. We describe here a scalable tissue-cultivation platform that is cell source agnostic and enables drug testing under electrical pacing. The plastic platform enabled on-line noninvasive recording of passive tension, active force, contractile dynamics, and Ca2+ transients, as well as endpoint assessments of action potentials and conduction velocity. By combining directed cell differentiation with electrical field conditioning, we engineered electrophysiologically distinct atrial and ventricular tissues with chamber-specific drug responses and gene expression. We report, for the first time, engineering of heteropolar cardiac tissues containing distinct atrial and ventricular ends, and we demonstrate their spatially confined responses to serotonin and ranolazine. Uniquely, electrical conditioning for up to 8 months enabled modeling of polygenic left ventricular hypertrophy starting from patient cells.

Keywords: Cardiomyocyte; action potential; atrial; calcium transient; contractility; drug testing; electrophysiology; heart; polygenic cardiac disease; tissue engineering; ventricular.

Publication types

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

MeSH terms

  • Action Potentials
  • Cell Differentiation
  • Cells, Cultured
  • Electrophysiological Phenomena
  • Humans
  • Induced Pluripotent Stem Cells / cytology
  • Models, Biological
  • Myocardium / cytology
  • Myocytes, Cardiac / cytology*
  • Myocytes, Cardiac / metabolism
  • Pluripotent Stem Cells / cytology
  • Tissue Culture Techniques / instrumentation*
  • Tissue Culture Techniques / methods
  • Tissue Engineering / methods*