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Assessment of Drug Proarrhythmic Potential in Electrically Paced Human Induced Pluripotent Stem Cell-Derived Ventricular Cardiomyocytes Using Multielectrode Array.
- Source :
-
SLAS discovery : advancing life sciences R & D [SLAS Discov] 2021 Mar; Vol. 26 (3), pp. 364-372. Date of Electronic Publication: 2020 Sep 11. - Publication Year :
- 2021
-
Abstract
- Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have been widely used for the assessment of drug proarrhythmic potential through multielectrode array (MEA). HiPSC-CM cultures beat spontaneously with a wide range of frequencies, however, which could affect drug-induced changes in repolarization. Pacing hiPSC-CMs at a physiological heart rate more closely resembles the state of in vivo ventricular myocytes and permits the standardization of test conditions to improve consistency. In this study, we systematically investigated the time window of stable ion currents in high-purity hiPSC-derived ventricular cardiomyocytes (hiPSC-vCMs) and confirmed that these cells could be used to correctly predict the proarrhythmic risk of Comprehensive In Vitro Proarrhythmia Assay (CiPA) reference compounds. To evaluate drug proarrhythmic potentials at a physiological beating rate, we used a MEA to electrically pace hiPSC-vCMs, and we recorded regular field potential waveforms in hiPSC-vCMs treated with DMSO and 10 CiPA reference drugs. Prolongation of field potential duration was detected in cells after exposure to high- and intermediate-risk drugs; in addition, drug-induced arrhythmia-like events were observed. The results of this study provide a simple and feasible method to investigate drug proarrhythmic potentials in hiPSC-CMs at a physiological beating rate.
- Subjects :
- Action Potentials physiology
Arrhythmias, Cardiac prevention & control
Calcium metabolism
Cations, Divalent
Cell Differentiation
Humans
Induced Pluripotent Stem Cells cytology
Ion Transport drug effects
Microelectrodes
Models, Biological
Myocardial Contraction drug effects
Myocytes, Cardiac cytology
Myocytes, Cardiac physiology
Nifedipine pharmacology
Patch-Clamp Techniques
Primary Cell Culture
Sotalol adverse effects
Tetrodotoxin antagonists & inhibitors
Tetrodotoxin toxicity
Verapamil pharmacology
Action Potentials drug effects
Anti-Arrhythmia Agents pharmacology
Induced Pluripotent Stem Cells physiology
Myocytes, Cardiac drug effects
Phenethylamines adverse effects
Quinidine adverse effects
Sulfonamides adverse effects
Subjects
Details
- Language :
- English
- ISSN :
- 2472-5560
- Volume :
- 26
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- SLAS discovery : advancing life sciences R & D
- Publication Type :
- Academic Journal
- Accession number :
- 32914673
- Full Text :
- https://doi.org/10.1177/2472555220953207