Center for Cardiovascular Research, The Abigail Wexner Research Institute and The Heart Center, Nationwide Children's Hospital, Columbus, Ohio, USA.
Department of Pediatrics, The Ohio State University College of Medicine, Columbus, Ohio, USA.
Stem Cells. 2020 Jul;38(7):822-833. doi: 10.1002/stem.3178. Epub 2020 Apr 27.
Patient-derived pluripotent stem cells (PSCs) have greatly transformed the current understanding of human heart development and cardiovascular disease. Cardiomyocytes derived from personalized PSCs are powerful tools for modeling heart disease and performing patient-based cardiac toxicity testing. However, these PSC-derived cardiomyocytes (PSC-CMs) are a mixed population of atrial-, ventricular-, and pacemaker-like cells in the dish, hindering the future of precision cardiovascular medicine. Recent insights gleaned from the developing heart have paved new avenues to refine subtype-specific cardiomyocytes from patients with known pathogenic genetic variants and clinical phenotypes. Here, we discuss the recent progress on generating subtype-specific (atrial, ventricular, and nodal) cardiomyocytes from the perspective of embryonic heart development and how human pluripotent stem cells will expand our current knowledge on molecular mechanisms of cardiovascular disease and the future of precision medicine.
患者来源的多能干细胞（PSCs）极大地改变了人们对人类心脏发育和心血管疾病的现有认识。源自个性化 PSCs 的心肌细胞是模拟心脏病和进行基于患者的心脏毒性测试的有力工具。然而，这些 PSC 衍生的心肌细胞（PSC-CMs）在培养皿中是一种混合的心房、心室和起搏样细胞群体，阻碍了精准心血管医学的未来发展。最近从发育中的心脏中获得的新见解为从具有已知致病性遗传变异和临床表型的患者中精细分离亚型特异性心肌细胞开辟了新途径。在这里，我们从胚胎心脏发育的角度讨论了从患者来源的多能干细胞中生成亚型特异性（心房、心室和结状）心肌细胞的最新进展，以及人类多能干细胞将如何扩展我们对心血管疾病分子机制的现有认识和精准医学的未来。
