2026-06-14T03:45:54Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/72202024-09-27T08:55:45Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
da Rocha, André Monteiro
author
Campbell, Katherine
author
Mironov, Sergey
author
Jiang, Jiang
author
Mundada, Lakshmi
author
Guerrero-Serna, Guadalupe
author
Jalife, Jose
author
Herron, Todd J
funder
National Institutes of Health (Estados Unidos)
funder
Lefkofsky Family Foundation
funder
UM Frankel Cardiovascular Center
2019-02-22T14:18:02Z
2019-02-22T14:18:02Z
2017-10-23
Sci Rep. 2017; 7(1):13834
10.1038/s41598-017-13590-y
2045-2322
2045-2322
Scientific reports
29061979
http://hdl.handle.net/20.500.12105/7220
Human 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.
eng
hiPSC-CM Monolayer Maturation State Determines Drug Responsiveness in High Throughput Pro-Arrhythmia Screen
journal article
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URL
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hiPSC-CMMonolayerMaturationState_2017_MOESM1_ESM.pdf
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hiPSC-CMMonolayerMaturationState_2017..pdf.txt
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hiPSC-CMMonolayerMaturationState_2017_MOESM1_ESM.pdf.txt