Moving beyond the comprehensive in vitro proarrhythmia assay: Use of human-induced pluripotent stem cell-derived cardiomyocytes to assess contractile effects associated with drug-induced structural cardiotoxicity

Journal of Applied Toxicology : JAT
Xi Yang, Thomas Papoian

Abstract

Drug-induced cardiotoxicity is a potentially severe side effect that can adversely affect myocardial contractility through structural or electrophysiological changes in cardiomyocytes. Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are a promising human cardiac in vitro model system to assess both proarrhythmic and non-proarrhythmic cardiotoxicity of new drug candidates. The scalable differentiation of hiPSCs into cardiomyocytes provides a renewable cell source that overcomes species differences present in current animal models of drug toxicity testing. The Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative represents a paradigm shift for proarrhythmic risk assessment, and hiPSC-CMs are an integral component of that paradigm. The recent advancements in hiPSC-CMs will not only impact safety decisions for possible drug-induced proarrhythmia, but should also facilitate risk assessment for non-proarrhythmic cardiotoxicity, where current non-clinical approaches are limited in detecting this risk before initiation of clinical trials. Importantly, emerging evidence strongly suggests that the use of hiPSC-CMs with cardiac physiological relevant measurements in vitro improves the detection of structural...Continue Reading

References

May 29, 2002·Fundamental & Clinical Pharmacology·Gerd BodeUNKNOWN ICH Expert Working Group
Dec 10, 2002·Science·G ManningS Sudarsanam
Sep 13, 2003·Pharmacology & Toxicology·Kendall B Wallace
Jul 18, 2006·Journal of Pharmacological and Toxicological Methods·Monika Skrzypiec-SpringRichard Schulz
Mar 14, 2007·Toxicological Sciences : an Official Journal of the Society of Toxicology·Brian D Guth
Apr 26, 2007·Nature Reviews. Cancer·Thomas ForceRichard A Van Etten
Apr 30, 2011·International Journal of Toxicology·R Dustan SarazanSyril Pettit
Jun 23, 2011·Toxicological Sciences : an Official Journal of the Society of Toxicology·Liang GuoKyle L Kolaja
Jul 5, 2011·Journal of Molecular and Cellular Cardiology·William E LouchBeata M Wolska
Aug 24, 2011·Toxicologic Pathology·Rafael Ponce
Nov 5, 2011·Stem Cells and Development·Joshua E BabiarzKyle L Kolaja
Jun 5, 2012·Journal of Pharmacological and Toxicological Methods·R Dustan SarazanBradley W Main
Jul 31, 2012·Toxicological Sciences : an Official Journal of the Society of Toxicology·Payal RanaYvonne Will
Dec 1, 2012·Nature Reviews. Drug Discovery·Joanne BowesSteven Whitebread
Jan 15, 2013·Toxicological Sciences : an Official Journal of the Society of Toxicology·Amy PointonJames E Sidaway
Mar 7, 2013·Stem Cells and Development·Scott D LundyMichael A Laflamme
Apr 3, 2013·Methods in Molecular Biology·Nasir Malik, Mahendra S Rao
May 28, 2013·Toxicology and Applied Pharmacology·Kimberly R DohertySarah Bacus
Sep 21, 2013·Toxicological Sciences : an Official Journal of the Society of Toxicology·Liang GuoKyle L Kolaja
Dec 26, 2013·Drug Discovery Today·Jorrit J HornbergTomas Mow
Feb 1, 2014·Circulation Research·Xiulan YangCharles E Murry
Apr 24, 2014·Journal of the American Heart Association·Virginia Shalkey HahnBonnie Ky
Jul 25, 2014·Toxicological Sciences : an Official Journal of the Society of Toxicology·Sandy EldridgeMyrtle Davis
Aug 6, 2014·Journal of Applied Toxicology : JAT·Yoko NishimuraTakeki Uehara
Sep 23, 2014·Toxicological Sciences : an Official Journal of the Society of Toxicology·Clay W ScottMatthew F Peters
Dec 30, 2014·Toxicological Sciences : an Official Journal of the Society of Toxicology·Amy PointonHelen Garside
Apr 7, 2015·Journal of Pharmacological and Toxicological Methods·Brian D GuthR Dustan Sarazan
Jun 1, 2015·Journal of Pharmacological and Toxicological Methods·Rob WallisHelen Maddock
Aug 12, 2015·Toxicological Sciences : an Official Journal of the Society of Toxicology·Mike ClementsSian Kalinka
Feb 20, 2016·Nature Reviews. Drug Discovery·Gary GintantNorman Stockbridge
Mar 25, 2016·Nature Reviews. Cardiology·Ian Y ChenJoseph C Wu

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Citations

Dec 12, 2018·Expert Opinion on Drug Metabolism & Toxicology·Ágota ApátiBalázs Sarkadi
Feb 11, 2020·Toxicological Sciences : an Official Journal of the Society of Toxicology·Jessica A PalmerRobert E Burrier
Nov 30, 2018·Frontiers in Pharmacology·Canan G Nebigil, Laurent Désaubry
May 12, 2020·Frontiers in Physiology·Sebastian MartewiczNicola Elvassore
Mar 20, 2021·Cell Chemical Biology·Anna P HnatiukMark Mercola
Jul 22, 2021·APL Bioengineering·Erika Ferrari, Marco Rasponi

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