BioMediTech, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
J Cardiovasc Pharmacol. 2020 Dec 15;77(3):300-316. doi: 10.1097/FJC.0000000000000972.
Despite major efforts by clinicians and researchers, cardiac arrhythmia remains a leading cause of morbidity and mortality in the world. Experimental work has relied on combining high-throughput strategies with standard molecular and electrophysiological studies, which are, to a great extent, based on the use of animal models. Because this poses major challenges for translation, the progress in the development of novel antiarrhythmic agents and clinical care has been mostly disappointing. Recently, the advent of human induced pluripotent stem cell-derived cardiomyocytes has opened new avenues for both basic cardiac research and drug discovery; now, there is an unlimited source of cardiomyocytes of human origin, both from healthy individuals and patients with cardiac diseases. Understanding arrhythmic mechanisms is one of the main use cases of human induced pluripotent stem cell-derived cardiomyocytes, in addition to pharmacological cardiotoxicity and efficacy testing, in vitro disease modeling, developing patient-specific models and personalized drugs, and regenerative medicine. Here, we review the advances that the human induced pluripotent stem cell-derived-based modeling systems have brought so far regarding the understanding of both arrhythmogenic triggers and substrates, while also briefly speculating about the possibilities in the future.
尽管临床医生和研究人员做出了巨大努力，但心律失常仍然是世界范围内发病率和死亡率的主要原因。实验工作依赖于将高通量策略与标准的分子和电生理研究相结合，而这些研究在很大程度上基于动物模型的使用。由于这给转化带来了重大挑战，新型抗心律失常药物的开发和临床治疗的进展大多令人失望。最近，人类诱导多能干细胞衍生的心肌细胞的出现为基础心脏研究和药物发现开辟了新的途径；现在，有无限来源的人类来源的心肌细胞，既有来自健康个体的，也有来自心脏病患者的。了解心律失常机制是人类诱导多能干细胞衍生心肌细胞的主要用途之一，除了药物的心脏毒性和疗效测试、体外疾病建模、开发患者特异性模型和个性化药物以及再生医学。在这里，我们回顾了基于人类诱导多能干细胞的建模系统在理解心律失常触发因素和基质方面带来的进展，同时也简要推测了未来的可能性。
