title: Functional differences in engineered myocardium from embryonic stem cell-derived versus neonatal cardiomyocytes.
abstract: 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.
authors.affiliation: Disease Biophysics Group, School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA ; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA ; Wyss Institute of Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA.
authors.forename: Adam W
authors.initials: AW
authors.lastname: Feinberg
authors.forename: Crystal M
authors.initials: CM
authors.lastname: Ripplinger
authors.forename: Peter
authors.initials: P
authors.lastname: van der Meer
authors.forename: Sean P
authors.initials: SP
authors.lastname: Sheehy
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Domian
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Chien
authors.forename: Kevin Kit
authors.initials: KK
authors.lastname: Parker
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000200:Action Potentials; D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D006352:Heart Ventricles / Q000166:cytology* / Q000196:embryology; D007365:Intercellular Junctions / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009200:Myocardial Contraction; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D023822:Tissue Engineering