12 April 2018 | Kacey Ronaldson-Bouchard, Stephen P. Ma, Keith Yeager, Timothy Chen, Loulin Song, Dario Sirabella, Kumi Morikawa, Diogo Teles, Masayuki Yazawa, Gordana Vunjak-Novakovic
This study demonstrates that human cardiac tissues can be matured from induced pluripotent stem cells (iPSCs) in just four weeks of in vitro culture. The tissues, formed from early-stage iPSC-derived cardiomyocytes and subjected to physical conditioning with increasing intensity, exhibited adult-like gene expression profiles, organized ultrastructure, physiological sarcomere length, and density of mitochondria. They also showed oxidative metabolism, a positive force–frequency relationship, and functional calcium handling. However, electromechanical properties developed more slowly and did not fully mature compared to adult human myocardium. The tissue maturity was necessary for achieving physiological responses to isoproterenol and recapitulating pathological hypertrophy, highlighting the utility of this model for studying cardiac development and disease. The study also highlights the importance of initiating physical conditioning early in the differentiation process and increasing the intensity of contractions to enhance maturation.This study demonstrates that human cardiac tissues can be matured from induced pluripotent stem cells (iPSCs) in just four weeks of in vitro culture. The tissues, formed from early-stage iPSC-derived cardiomyocytes and subjected to physical conditioning with increasing intensity, exhibited adult-like gene expression profiles, organized ultrastructure, physiological sarcomere length, and density of mitochondria. They also showed oxidative metabolism, a positive force–frequency relationship, and functional calcium handling. However, electromechanical properties developed more slowly and did not fully mature compared to adult human myocardium. The tissue maturity was necessary for achieving physiological responses to isoproterenol and recapitulating pathological hypertrophy, highlighting the utility of this model for studying cardiac development and disease. The study also highlights the importance of initiating physical conditioning early in the differentiation process and increasing the intensity of contractions to enhance maturation.