Merits of hiPSC-Derived Cardiomyocytes for In Vitro Research and Testing Drug Toxicity

Abstract

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.