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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.

SUBMITTER: Feinberg AW 

PROVIDER: S-EPMC3841251 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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

Feinberg Adam W AW   Ripplinger Crystal M CM   van der Meer Peter P   Sheehy Sean P SP   Domian Ibrahim I   Chien Kenneth R KR   Parker Kevin Kit KK  

Stem cell reports 20131107 5


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 embryon  ...[more]

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