دورية أكاديمية
International Multisite Study of Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes for Drug Proarrhythmic Potential Assessment.
| العنوان: | International Multisite Study of Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes for Drug Proarrhythmic Potential Assessment. |
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| المؤلفون: | Blinova, Ksenia, Dang, Qianyu, Millard, Daniel, Smith, Godfrey, Pierson, Jennifer, Guo, Liang, Brock, Mathew, Lu, Hua Rong, Kraushaar, Udo, Zeng, Haoyu, Shi, Hong, Zhang, Xiaoyu, Sawada, Kohei, Osada, Tomoharu, Kanda, Yasunari, Sekino, Yuko, Pang, Li, Feaster, Tromondae K, Kettenhofen, Ralf, Stockbridge, Norman, Strauss, David G, Gintant, Gary |
| المصدر: | Cell Rep ; ISSN:2211-1247 ; Volume:24 ; Issue:13 |
| بيانات النشر: | Elsevier Science |
| سنة النشر: | 2018 |
| المجموعة: | PubMed Central (PMC) |
| مصطلحات موضوعية: | CiPA, comprehensive in vitro proarrhythmia assay, drug-induced ventricular arrhythmia Torsade de Pointes, hiPSC-CM, human-induced pluripotent stem cell-derived cardiomycotes, microelectrode array, voltage-sensitive dyes |
| الوصف: | To assess the utility of human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) as an in vitro proarrhythmia model, we evaluated the concentration dependence and sources of variability of electrophysiologic responses to 28 drugs linked to low, intermediate, and high torsades de pointes (TdP) risk categories using two commercial cell lines and standardized protocols in a blinded multisite study using multielectrode array or voltage-sensing optical approaches. Logistical and ordinal linear regression models were constructed using drug responses as predictors and TdP risk categories as outcomes. Three of seven predictors (drug-induced arrhythmia-like events and prolongation of repolarization at either maximum tested or maximal clinical exposures) categorized drugs with reasonable accuracy (area under the curve values of receiver operator curves ∼0.8). hiPSC-CM line, test site, and platform had minimal influence on drug categorization. These results demonstrate the utility of hiPSC-CMs to detect drug-induced proarrhythmic effects as part of the evolving Comprehensive In Vitro Proarrhythmia Assay paradigm. |
| نوع الوثيقة: | article in journal/newspaper report |
| اللغة: | English |
| العلاقة: | https://doi.org/10.1016/j.celrep.2018.08.079Test; https://pubmed.ncbi.nlm.nih.gov/30257217Test; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6226030Test/ |
| DOI: | 10.1016/j.celrep.2018.08.079 |
| الإتاحة: | https://doi.org/10.1016/j.celrep.2018.08.079Test https://pubmed.ncbi.nlm.nih.gov/30257217Test https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6226030Test/ |
| حقوق: | Published by Elsevier Inc. |
| رقم الانضمام: | edsbas.539A0CA9 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/j.celrep.2018.08.079 |
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