Functional differences in engineered myocardium from embryonic stem cell-derived versus neonatal cardiomyocytes

Stem Cell Reports. 2013 Nov 7;1(5):387-96. doi: 10.1016/j.stemcr.2013.10.004. eCollection 2013.


Stem cell-derived cardiomyocytes represent unique tools for cell- and tissue-based regenerative therapies, drug discovery and safety, and studies of fundamental heart-failure mechanisms. However, the degree to which stem cell-derived cardiomyocytes compare to mature cardiomyocytes is often debated. We reasoned that physiological metrics of engineered cardiac tissues offer a means of comparison. We built laminar myocardium engineered from cardiomyocytes that were differentiated from mouse embryonic stem cell-derived cardiac progenitors or harvested directly from neonatal mouse ventricles, and compared their anatomy and physiology in vitro. Tissues assembled from progenitor-derived myocytes and neonate myocytes demonstrated similar cytoskeletal architectures but different gap junction organization and electromechanical properties. Progenitor-derived myocardium had significantly less contractile stress and slower longitudinal conduction velocity than neonate-derived myocardium, indicating that the developmental state of the cardiomyocytes affects the electromechanical function of the resultant engineered tissue. These data suggest a need to establish performance metrics for future stem cell applications.

Publication types

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

MeSH terms

  • Actin Cytoskeleton / metabolism
  • Action Potentials*
  • Animals
  • Cell Differentiation*
  • Cells, Cultured
  • Embryonic Stem Cells / cytology*
  • Embryonic Stem Cells / metabolism
  • Embryonic Stem Cells / physiology
  • Heart Ventricles / cytology*
  • Heart Ventricles / embryology
  • Intercellular Junctions / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Myocardial Contraction*
  • Myocytes, Cardiac / cytology
  • Myocytes, Cardiac / metabolism
  • Myocytes, Cardiac / physiology*
  • Tissue Engineering