title: In vitro pharmacologic testing using human induced pluripotent stem cell-derived cardiomyocytes.
abstract: The lethal ventricular arrhythmia Torsade de pointes (TdP) is the most common reason for the withdrawal or restricted use of many cardiovascular and non-cardiovascular drugs. The lack of an in vitro model to detect pro-arrhythmic effects on human heart cells hinders the development of new drugs. We hypothesized that recently established human induced pluripotent stem (hiPS) cells could be used in an in vitro drug screening model. In this study, hiPS cells were driven to differentiate into functional cardiomyocytes, which expressed cardiac markers including Nkx2.5, GATA4, and atrial natriuretic peptide. The hiPS-derived cardiomyocytes (hiPS-CMs) were analyzed using a multi electrode assay. The application of ion channel inhibitors resulted in dose-dependent changes to the field potential waveform, and these changes were identical to those induced in the native cardiomyocytes. This study shows that hiPS-CMs represent a promising in vitro model for cardiac electrophysiologic studies and drug screening.
authors.affiliation: Department of Regenerative Medicine and Advanced Cardiac Therapeutics, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Tomofumi
authors.initials: T
authors.lastname: Tanaka
authors.forename: Shugo
authors.initials: S
authors.lastname: Tohyama
authors.forename: Mitsushige
authors.initials: M
authors.lastname: Murata
authors.forename: Fumimasa
authors.initials: F
authors.lastname: Nomura
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Kaneko
authors.forename: Hao
authors.initials: H
authors.lastname: Chen
authors.forename: Fumiyuki
authors.initials: F
authors.lastname: Hattori
authors.forename: Toru
authors.initials: T
authors.lastname: Egashira
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Seki
authors.forename: Yohei
authors.initials: Y
authors.lastname: Ohno
authors.forename: Uichi
authors.initials: U
authors.lastname: Koshimizu
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Yuasa
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ogawa
authors.forename: Shinya
authors.initials: S
authors.lastname: Yamanaka
authors.forename: Kenji
authors.initials: K
authors.lastname: Yasuda
authors.forename: Keiichi
authors.initials: K
authors.lastname: Fukuda
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D009320:Atrial Natriuretic Factor / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D004353:Drug Evaluation, Preclinical / Q000379:methods; D050991:GATA4 Transcription Factor / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D006321:Heart / Q000502:physiology; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D007473:Ion Channels / Q000037:antagonists & inhibitors / Q000235:genetics; D007545:Isoproterenol / Q000494:pharmacology; D032383:Myocytes, Cardiac / Q000166:cytology*; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000187:drug effects; D014157:Transcription Factors / Q000235:genetics
chemical_list: D000318:Adrenergic beta-Agonists; D050991:GATA4 Transcription Factor; C484170:GATA4 protein, human; D005819:Genetic Markers; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; D007473:Ion Channels; C095552:NKX2-5 protein, human; D014157:Transcription Factors; D009320:Atrial Natriuretic Factor; D007545:Isoproterenol