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dc.contributor.authorda Rocha, André Monteiro
dc.contributor.authorCampbell, Katherine
dc.contributor.authorMironov, Sergey
dc.contributor.authorJiang, Jiang
dc.contributor.authorMundada, Lakshmi
dc.contributor.authorGuerrero-Serna, Guadalupe
dc.contributor.authorJalife, Jose 
dc.contributor.authorHerron, Todd J
dc.identifier.citationSci Rep. 2017; 7(1):13834es_ES
dc.description.abstractHuman induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) offer a novel in vitro platform for pre-clinical cardiotoxicity and pro-arrhythmia screening of drugs in development. To date hiPSC-CMs used for cardiotoxicity testing display an immature, fetal-like cardiomyocyte structural and electrophysiological phenotype which has called into question the applicability of hiPSC-CM findings to the adult heart. The aim of the current work was to determine the effect of cardiomyocyte maturation state on hiPSC-CM drug responsiveness. To this end, here we developed a high content pro-arrhythmia screening platform consisting of either fetal-like or mature hiPSC-CM monolayers. Compounds tested in the screen were selected based on the pro-arrhythmia risk classification (Low risk, Intermediate risk, or High risk) established recently by the FDA and major stakeholders in the Drug Discovery field for the validation of the Comprehensive In vitro Pro-Arrhythmia Assay (CiPA). Here we show that maturation state of hiPSC-CMs determines the absolute pro-arrhythmia risk score calculated for these compounds. Thus, the maturation state of hiPSC-CMs should be considered prior to pro-arrhythmia and cardiotoxicity screening in drug discovery programs.es_ES
dc.description.sponsorshipResearch reported in this publication was supported by the National Institute of Environmental Health Sciences of the National Institutes of Health under Award Number R43ES027703. This study was also supported by the Lefkofsky Family Foundation (T.J.H.), the UM Frankel Cardiovascular Center (T.J.H.), and the State of Michigan Economic Development Fund (U-M Michigan Translational Research and Commercialization for Life Sciences Program [U-M MTRAC], T.J.H. and J.J.)es_ES
dc.publisherNature Publishing Group es_ES
dc.titlehiPSC-CM Monolayer Maturation State Determines Drug Responsiveness in High Throughput Pro-Arrhythmia Screenes_ES
dc.typejournal articlees_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.contributor.funderNational Institutes of Health (Estados Unidos) 
dc.contributor.funderLefkofsky Family Foundation 
dc.contributor.funderUM Frankel Cardiovascular Center
dc.identifier.journalScientific reportses_ES
dc.repisalud.orgCNICCNIC::Grupos de investigación::Arritmias Cardíacases_ES
dc.rights.accessRightsopen accesses_ES

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