AUTHOR=Martewicz Sebastian , Magnussen Michael , Elvassore Nicola TITLE=Beyond Family: Modeling Non-hereditary Heart Diseases With Human Pluripotent Stem Cell-Derived Cardiomyocytes JOURNAL=Frontiers in Physiology VOLUME=11 YEAR=2020 URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2020.00384 DOI=10.3389/fphys.2020.00384 ISSN=1664-042X ABSTRACT=

Non-genetic cardiac pathologies develop as an aftermath of extracellular stress-conditions. Nevertheless, the response to pathological stimuli depends deeply on intracellular factors such as physiological state and complex genetic backgrounds. Without a thorough characterization of their in vitro phenotype, modeling of maladaptive hypertrophy, ischemia and reperfusion injury or diabetes in human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) has been more challenging than hereditary diseases with defined molecular causes. In past years, greater insights into hPSC-CM in vitro physiology and advancements in technological solutions and culture protocols have generated cell types displaying stress-responsive phenotypes reminiscent of in vivo pathological events, unlocking their application as a reductionist model of human cardiomyocytes, if not the adult human myocardium. Here, we provide an overview of the available literature of pathology models for cardiac non-genetic conditions employing healthy (or asymptomatic) hPSC-CMs. In terms of numbers of published articles, these models are significantly lagging behind monogenic diseases, which misrepresents the incidence of heart disease causes in the human population.