Martewicz Sebastian, Magnussen Michael, Elvassore Nicola
Shanghai Institute for Advanced Immunochemical Studies (SIAIS), ShanghaiTech University, Shanghai, China.
Stem Cells & Regenerative Medicine Section, UCL Great Ormond Street Institute of Child Health, London, United Kingdom.
Front Physiol. 2020 Apr 22;11:384. doi: 10.3389/fphys.2020.00384. eCollection 2020.
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 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 physiology and advancements in technological solutions and culture protocols have generated cell types displaying stress-responsive phenotypes reminiscent of 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.
非遗传性心脏病理状况是细胞外应激条件的后果。然而，对病理刺激的反应在很大程度上取决于细胞内因素，如生理状态和复杂的遗传背景。如果没有对其表型进行全面表征，在人类多能干细胞衍生的心肌细胞（hPSC-CMs）中模拟适应性肥大、缺血再灌注损伤或糖尿病比具有明确分子病因的遗传性疾病更具挑战性。在过去几年中，对hPSC-CM生理学的更深入了解以及技术解决方案和培养方案的进步，产生了显示出应激反应表型的细胞类型，这些表型让人联想到病理事件，从而开启了它们作为人类心肌细胞（即使不是成人心肌）的简化模型的应用。在这里，我们概述了使用健康（或无症状）hPSC-CMs的心脏非遗传疾病病理模型的现有文献。就已发表文章的数量而言，这些模型明显落后于单基因疾病，这歪曲了人群中心脏病病因的发生率。
