Advanced maturation of human cardiac tissue grown from pluripotent stem cells

Advanced maturation of human cardiac tissue grown from pluripotent stem cells

12 APRIL 2018 | Kacey Ronaldson-Bouchard, Stephen P. Ma, Keith Yeager, Timothy Chen, Loujin Song, Dario Sirabella, Kumi Morikawa, Diogo Teles, Masayuki Yazawa, Gordana Vunjak-Novakovic
Researchers have developed a method to create adult-like human cardiac tissue from pluripotent stem cells (iPSCs) in just four weeks. By using early-stage iPSC-derived cardiomyocytes and subjecting them to increasing intensity of electrical stimulation, the tissue exhibits adult-like gene expression, ultrastructure, sarcomere length, mitochondrial density, transverse tubules, oxidative metabolism, and a positive force-frequency relationship. These tissues also display physiological calcium handling and electromechanical properties, though they do not fully replicate the maturity of adult human myocardium. The study highlights the importance of early mechanical conditioning to achieve physiological responses to isoproterenol and to recapitulate pathological hypertrophy. The tissue model offers a valuable tool for studying cardiac development and disease. The research demonstrates that the maturation of cardiac tissue can be accelerated through physical conditioning, mimicking the mechanical loading during fetal-to-postnatal transition. The tissues developed adult-like gene expression and ultrastructure, oxidative metabolism, and physiological calcium handling. However, the maturation period of four weeks may be too short to fully establish all functional features of adult myocardium. The study also shows that T-tubules and oxidative metabolism are essential for physiological force-frequency relationships and calcium handling. The tissue model does not fully replicate the macroscopic structure of the myocardium, which may explain the contrast between the impressive morphological maturation and the less complete functional maturation. The study suggests that this human cardiac tissue model could be useful for studying the progression of functional maturation.Researchers have developed a method to create adult-like human cardiac tissue from pluripotent stem cells (iPSCs) in just four weeks. By using early-stage iPSC-derived cardiomyocytes and subjecting them to increasing intensity of electrical stimulation, the tissue exhibits adult-like gene expression, ultrastructure, sarcomere length, mitochondrial density, transverse tubules, oxidative metabolism, and a positive force-frequency relationship. These tissues also display physiological calcium handling and electromechanical properties, though they do not fully replicate the maturity of adult human myocardium. The study highlights the importance of early mechanical conditioning to achieve physiological responses to isoproterenol and to recapitulate pathological hypertrophy. The tissue model offers a valuable tool for studying cardiac development and disease. The research demonstrates that the maturation of cardiac tissue can be accelerated through physical conditioning, mimicking the mechanical loading during fetal-to-postnatal transition. The tissues developed adult-like gene expression and ultrastructure, oxidative metabolism, and physiological calcium handling. However, the maturation period of four weeks may be too short to fully establish all functional features of adult myocardium. The study also shows that T-tubules and oxidative metabolism are essential for physiological force-frequency relationships and calcium handling. The tissue model does not fully replicate the macroscopic structure of the myocardium, which may explain the contrast between the impressive morphological maturation and the less complete functional maturation. The study suggests that this human cardiac tissue model could be useful for studying the progression of functional maturation.
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[slides and audio] Advanced maturation of human cardiac tissue grown from pluripotent stem cells