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Evaluation of in vitro models of stem cell-derived cardiomyocytes to screen for potential cardiotoxicity of chemicals

Shi, Miaoying ; Tien, Nguyen T. ; de Haan, Laura ; Louisse, Jochem ; Rietjens, Ivonne M.C.M. ; Bouwmeester, Hans

Toxicology in vitro, 2020-09, Vol.67, p.104891, Article 104891 [Periódico revisado por pares]

England: Elsevier Ltd

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Título:
Evaluation of in vitro models of stem cell-derived cardiomyocytes to screen for potential cardiotoxicity of chemicals
Autor: Shi, Miaoying ; Tien, Nguyen T. ; de Haan, Laura ; Louisse, Jochem ; Rietjens, Ivonne M.C.M. ; Bouwmeester, Hans
Assuntos: Adrenergic receptors ; Animals ; Assaying ; Calcium ; Calcium channel blockers ; Cardiomyocytes ; Cardiotoxicity ; Cardiotoxins - toxicity ; Cell culture ; Cells, Cultured ; Chemicals ; Clinical data ; Drug Evaluation, Preclinical - methods ; Evaluation ; Human induced pluripotent stem cell-derived cardiomyocytes ; Induced Pluripotent Stem Cells - cytology ; Mice ; Models, Biological ; Mouse embryonic stem cell-derived cardiomyocytes ; Mouse Embryonic Stem Cells - cytology ; Multi-electrode array ; Myocytes, Cardiac - drug effects ; Myocytes, Cardiac - physiology ; Na+/K+-exchanging ATPase ; Pharmacovigilance ; Pluripotency ; Potassium ; Screening ; Sodium ; Stem cells
É parte de: Toxicology in vitro, 2020-09, Vol.67, p.104891, Article 104891
Descrição: Cardiotoxicity is an important toxicological endpoint for chemical and drug safety assessment. The present study aims to evaluate two stemcell-based in vitro models for cardiotoxicity screening of chemicals. Eleven model compounds were used to evaluate responses of mouse embryonic stem cell-derived cardiomyocytes (mESC-CMs) using beating arrest as a readout and the analysis of electrophysiological parameters measured with a multi-electrode array (MEA) platform of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Results revealed that the hiPSC-CM MEA assay responded to all compounds. The mESC-CM beating arrest assay was not responsive to potassium channel blockers and showed a lower sensitivity to sodium channel blockers and Na+/K+ ATPase inhibitors compared to the hiPSC-CM MEA assay. Calcium channel blockers and a β-adrenergic receptor agonist showed comparable potencies in both models. The in vitro response concentrations from hiPSC-CMs were highly concordant with human effective serum concentrations of potassium and sodium channel blockers. It is concluded that both in vitro models enable the cardiotoxicity screening with different applicability domains. The mESC-CM beating arrest assay may be used as a first step in a tiered approach while the hiPSC-CM MEA assay may be the best starting point for quantitative in vitro to in vivo extrapolations. •Mouse and human stem cell-based in vitro models for cardiotoxicity were evaluated.•The in vitro models show mode-of-action dependent differences in sensitivity.•The in vitro hiPSC-CMs responses correlate well with human clinical data.•hiPSC-CM MEA assay can be a basis for quantitative in vitro in vivo extrapolation.
Editor: England: Elsevier Ltd
Idioma: Inglês

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Evaluation of in vitro models of stem cell-derived cardiomyocytes to screen for potential cardiotoxicity of chemicals

Shi, Miaoying ; Tien, Nguyen T. ; de Haan, Laura ; Louisse, Jochem ; Rietjens, Ivonne M.C.M. ; Bouwmeester, Hans

England: Elsevier Ltd

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