title: Expanding mouse ventricular cardiomyocytes through GSK-3 inhibition.
abstract: Controlled proliferation of cardiomyocytes remains a major limitation in cell biology and one of the main underlying hurdles for true modern regenerative medicine. Here, a technique is described for robust expansion of early fetal-derived mouse ventricular cardiomyocytes on a platform usable for high-throughput molecular screening, tissue engineering and, potentially, in vivo translational experiments. This method provides a small-molecule approach to control proliferation or differentiation of early beating cardiomyocytes through modulation of the Wnt/β-catenin signaling pathway. Moreover, isolation and expansion of fetal cardiomyocytes takes less than 3 weeks, yields a relatively pure (∼70%) functional myogenic population, and is highly reproducible.
authors: Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts.|Harvard Medical School, Boston, Massachusetts.|Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors: Jan W
authors: JW
authors: Buikema
authors: Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts.|Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors: Peter-Paul M
authors: PM
authors: Zwetsloot
authors: Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors: Pieter A
authors: PA
authors: Doevendans
authors: Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors: Joost P G
authors: JPG
authors: Sluijter
authors: Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts.|Harvard Medical School, Boston, Massachusetts.|Harvard Stem Cell Institute, Cambridge, Massachusetts.
authors: Ibrahim J
authors: IJ
authors: Domian
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D005333:Fetus; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors*; D006352:Heart Ventricles / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000502:physiology; D011247:Pregnancy; D011725:Pyridines / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D044968:Regenerative Medicine; D015203:Reproducibility of Results
chemical_list: C473711:Chir 99021; D011725:Pyridines; D011743:Pyrimidines; D038362:Glycogen Synthase Kinase 3
keywords: GSK-3 inhibitor; Wnt/β-catenin signaling; cardiomyocyte proliferation; differentiation; expansion; isolation