Use of Human Pluripotent Stem Cell Derived‐Cardiomyocytes to Study Drug‐Induced Cardiotoxicity. Issue 1 (4th August 2017)

• Record Type: Journal Article
• Authors: Maillet, Agnes; Tan, Kim Peng; Brunham, Liam R.
• Editors: Costa, Lucio G; Davila, Julio C.; Lawrence, David A.; Reed, Donald J.
• Is Part Of: Current protocols in toxicology. Volume 73:Issue 1(2017)
• Page Start: 22.5.1
• Page End: 22.5.22
• Publication Date: 2017-08-04
• Subjects: genome‐editing -- differentiation -- cardiomyocytes -- cardiotoxicity -- functional tests; Toxicology -- Laboratory manuals; Toxicology -- methods; Toxicology; Laboratory Manual; Electronic books; Laboratory manuals; 571.95028
• DOI: 10.1002/cptx.30
• Languages: English
• ISSNs: 1934-9254

Abstract

Abstract: Drug‐induced cardiotoxicity is the one of the most common causes of drug withdrawal from market. A major barrier in managing the risk of drug‐induced cardiotoxicity has been the lack of relevant models to study cardiac safety. Human pluripotent stem cell‐derived cardiomyocytes (hPSC‐CMs) have great potential in drug discovery and cardiotoxcity screens as they display many characteristics of the human myocardium and offer unlimited supply. This unit describes how to use pluripotent stem cells derived cardiomyocytes to study drug‐induced cardiotoxicty using doxorubicin as an example. We present a workflow that explains procedure for editing hPSC using the CRISPR/Cas9 system and for differentiation of hPSC into cardiomyocytes. We also report protocols to study drug effect on ROS production, intracellular calcium concentration, formation of DNA double strand breaks, gene expression and electrophysiological properties of hPSC‐CMs. © 2017 by John Wiley & Sons, Inc.