CSAHi study: Validation of multi-electrode array systems (MEA60/2100) for prediction of drug-induced proarrhythmia using human iPS cell-derived cardiomyocytes -assessment of inter-facility and cells lot-to-lot-variability

Autor: Hiroko Endo, Junko Shinozaki, Kaori Miyamoto, Chiho Nagasawa, Hitoshi Watanabe, Shinobu Suzuki, Shota Saiki, Chiaki Nakamori, Kiyotaka Koyabu, Yayoi Honda, Chiaki Nakayama, Ikumi Washio, Takeshi Kunimatsu, Hisashi Nogawa, Hiroshi Iwasaki, Etsushi Takahashi, Yumiko Nozaki, Atsuhiro Yamanishi, Tetsuji Itoh
Rok vydání: 2016
Předmět:
0301 basic medicine
Drug
ERG1 Potassium Channel
medicine.medical_specialty
media_common.quotation_subject
Induced Pluripotent Stem Cells
hERG
Cell Culture Techniques
Action Potentials
Observation
Toxicology
Risk Assessment
030226 pharmacology & pharmacy
QT interval
03 medical and health sciences
0302 clinical medicine
Japan
Heart Rate
Internal medicine
Toxicity Tests
Potassium Channel Blockers
medicine
Electrode array
Humans
Myocytes
Cardiac
Cells
Cultured
media_common
Proarrhythmia
Cardiotoxicity
Dose-Response Relationship
Drug
biology
Cardiac cycle
business.industry
Reproducibility of Results
Arrhythmias
Cardiac
Cell Differentiation
Potassium channel blocker
Equipment Design
General Medicine
medicine.disease
030104 developmental biology
biology.protein
Cardiology
Biological Assay
business
Microelectrodes
medicine.drug
Zdroj: Regulatory Toxicology and Pharmacology. 77:75-86
ISSN: 0273-2300
DOI: 10.1016/j.yrtph.2016.02.007
Popis: In vitro screening of hERG channels are recommended under ICH S7B guidelines to predict drug-induced QT prolongation and Torsade de Pointes (TdP), whereas proarrhythmia is known to be evoked by blockage of other ion channels involved in cardiac contraction and compensation mechanisms. A consortium for drug safety assessment using human iPS cells-derived cardiomyocytes (hiPS-CMs), CSAHi, has been organized to establish a novel in vitro test system that would enable better prediction of drug-induced proarrhythmia and QT prolongation. Here we report the inter-facility and cells lot-to-lot variability evaluated with FPDc (corrected field potential duration), FPDc10 (10% FPDc change concentration), beat rate and incidence of arrhythmia-like waveform or arrest on hiPS-CMs in a multi-electrode array system. Arrhythmia-like waveforms were evident for all test compounds, other than chromanol 293B, that evoked FPDc prolongation in this system and are reported to induce TdP in clinical practice. There was no apparent cells lot-to-lot variability, while inter-facility variabilities were limited within ranges from 3.9- to 20-folds for FPDc10 and about 10-folds for the minimum concentration inducing arrhythmia-like waveform or arrests. In conclusion, the new assay model reported here would enable accurate prediction of a drug potential for proarrhythmia.
Databáze: OpenAIRE
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