Human induced pluripotent stem cell (iPSC)-derived cardiomyocytes as an in vitro model in toxicology: strengths and weaknesses for hazard identification and risk characterization

被引:36
作者
Burnett, Sarah D. [1 ]
Blanchette, Alexander D. [1 ]
Chiu, Weihsueh A. [1 ]
Rusyn, Ivan [1 ]
机构
[1] Texas A&M Univ, Dept Vet Integrat Biosci, College Stn, TX 77843 USA
基金
美国国家卫生研究院;
关键词
Cardiotoxicity; new approach methods; drugs; environmental chemicals; HUMAN IPS CELLS; CARDIOTOXICITY ASSESSMENT; PATHOGENESIS;
D O I
10.1080/17425255.2021.1894122
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Introduction Human induced pluripotent stem cell (iPSC)-derived cardiomyocytes is one of the most widely used cell-based models that resulted from the discovery of how non-embryonic stem cells can be differentiated into multiple cell types. In just one decade, iPSC-derived cardiomyocytes went from a research lab to widespread use in biomedical research and preclinical safety evaluation for drugs and other chemicals. Areas covered This manuscript reviews data on toxicology applications of human iPSC-derived cardiomyocytes. We detail the outcome of a systematic literature search on their use (i) in hazard assessment for cardiotoxicity liabilities, (ii) for risk characterization, (iii) as models for population variability, and (iv) in studies of personalized medicine and disease. Expert opinion iPSC-derived cardiomyocytes are useful to increase the accuracy, precision, and efficiency of cardiotoxicity hazard identification for both drugs and non-pharmaceuticals, with recent efforts beginning to demonstrate their utility for risk characterization. Notable limitations include the needs to improve the maturation of cells in culture, to better understand their potential use identifying structural cardiotoxicity, and for additional case studies involving population-wide and disease-specific risk characterization. Ultimately, the greatest future benefits are likely for non-pharmaceutical chemicals, filling a critical gap where no routine testing for cardiotoxicity is currently performed.
引用
收藏
页码:887 / 902
页数:16
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