Wang Ping-Hsien, Fang Yi-Hsien, Liu Yen-Wen, Yeh Min-Long
Department of Biomedical Engineering, National Cheng Kung University, Tainan 70140, Taiwan.
Division of Cardiology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70403, Taiwan.
Biomedicines. 2022 Oct 31;10(11):2764. doi: 10.3390/biomedicines10112764.
The progress of medical technology and scientific advances in the field of anticancer treatment have increased the survival probabilities and duration of life of patients. However, cancer-therapy-induced cardiac dysfunction remains a clinically salient problem. Effective anticancer therapies may eventually induce cardiomyopathy. To date, several studies have focused on the mechanisms underlying cancer-treatment-related cardiotoxicity. Cardiomyocyte cell lines with no contractile physiological characteristics cannot adequately model "true" human cardiomyocytes. However, applying "true" human cardiomyocytes for research is fraught with many obstacles (e.g., invasiveness of the procedure), and there is a proliferative limitation for rodent primary cultures. Human-induced pluripotent stem-cell-differentiated cardiomyocytes (hiPSC-CMs), which can be produced efficiently, are viable candidates for mimicking human cardiomyocytes in vitro. We successfully performed cardiac differentiation of human iPSCs to obtain hiPSC-CMs. These hiPSC-CMs can be used to investigate the pathophysiological basis and molecular mechanism of cancer-treatment-related cardiotoxicity and to develop novel strategies to prevent and rescue such cardiotoxicity. We propose that hiPSC-CMs can be used as an in vitro drug screening platform to study targeted cancer-therapy-related cardiotoxicity.
医学技术的进步以及抗癌治疗领域的科学进展提高了患者的生存概率和寿命。然而，癌症治疗引起的心脏功能障碍仍然是一个临床上突出的问题。有效的抗癌治疗最终可能会诱发心肌病。迄今为止，已有多项研究聚焦于癌症治疗相关心脏毒性的潜在机制。没有收缩生理特性的心肌细胞系无法充分模拟“真正的”人类心肌细胞。然而，将“真正的”人类心肌细胞应用于研究充满了许多障碍（例如，操作的侵入性），并且啮齿动物原代培养存在增殖限制。能够高效产生的人诱导多能干细胞分化心肌细胞（hiPSC-CMs）是在体外模拟人类心肌细胞的可行候选者。我们成功地对人诱导多能干细胞进行了心脏分化以获得hiPSC-CMs。这些hiPSC-CMs可用于研究癌症治疗相关心脏毒性的病理生理基础和分子机制，并开发预防和挽救此类心脏毒性的新策略。我们提出，hiPSC-CMs可作为体外药物筛选平台来研究靶向癌症治疗相关的心脏毒性。
