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The Application of Human Embryonic Stem Cells and Human Induced Pluripotent Stem Cells Derived Cardiomyocytes on Cardiotoxicity Screening
Wang Shuyan1, Wang Xijie1, Han Ling2, Ma Jing1*
1Shanghai Institute of Pharmaceutical Industry National Shanghai Center for New Drug Safety Evaluation & Research State Institute of Pharmaceutical Industry, Shanghai 201203, China; 2Center for Drug Evaluation State Food and Drug Adm
Abstract: Cardiovascular toxicity is one of the main reasons of the failure of the drug development， which is also a difficult problem in preclinical safety evaluation experiment. The unlimited proliferation， self-renewal， multi-directional differentiation properties of human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs) provide cell resources in vitro cardiac toxicity screening experiment. hESC and hiPSCs derived cardiomyocytes have been reported to share a high degree of similarity in morphology structure， and over time the density of functional potassium， sodium， calcium channels gradually increase， the key cardiac structural and functional genes ANF， α-MHC， MLC-2a robustly upregulate， electtophysiological and biochemical characteristics are similar. These characteristics are similar to that of immature cardiomyocytes. The applications of hESCs and hiPSCs in drug screening， includin g ion channels， action potentials， biomarkers of cardiotoxicity and contraction， and these demonstrated pharmacologic responses similar to those in clinical observations. Establishment of the model in vitro reduces the time and the cost， overcomes the problem of species specificity and promotes the development of cardiotoxicity.
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