Turnbull Irene C, Lieu Deborah K, Li Ronald A, Costa Kevin D
Cardiovascular Research Center, Mount Sinai School of Medicine, New York, NY.
Department of Internal Medicine, Division of Cardiovascular Medicine, University of California, Davis, CA.
Drug Discov Today Dis Models. 2012 Winter;9(4):e219-e227. doi: 10.1016/j.ddmod.2012.11.001. Epub 2012 Dec 21.
Cardiovascular disease (CVD) is the most prevalent health problem in the world, and the high mortality rate associated with irreversibly injured heart muscle motivates an urgent need for the development of novel therapies to treat damaged myocardium. Recently, human engineered cardiac tissues (hECT) have been created using cardiomyocytes derived from human embryonic stem cells and human induced pluripotent stem cells. Although a healthy adult phenotype remains elusive, such hECT display structural and functional properties that recapitulate key aspects of natural human myocardium, including dose related responses to compounds with known chronotropic, inotropic and arrhythmogenic effects. Thus, hECT offer the advantage over traditional culture models of providing a biomimetic 3D environment for the study of myocardial physiopathology, and may be used to generate preclinical models for the development and screening of therapies for CVD.
心血管疾病(CVD)是全球最普遍的健康问题,与不可逆损伤心肌相关的高死亡率促使人们迫切需要开发新的疗法来治疗受损心肌。最近,利用源自人类胚胎干细胞和人类诱导多能干细胞的心肌细胞创建了人类工程心脏组织(hECT)。尽管健康的成年表型仍然难以实现,但此类hECT显示出结构和功能特性,概括了天然人类心肌的关键方面,包括对具有已知变时性、变力性和致心律失常作用的化合物的剂量相关反应。因此,hECT相对于传统培养模型具有优势,可为心肌生理病理学研究提供仿生3D环境,并可用于生成用于CVD治疗开发和筛选的临床前模型。