In vitro pharmacologic testing using human induced pluripotent stem cell-derived cardiomyocytes

Tomofumi Tanaka, Shugo Tohyama, Mitsushige Murata, Fumimasa Nomura, Tomoyuki Kaneko, Hao Chen, Fumiyuki Hattori, Toru Egashira, Tomohisa Seki, Yohei Ohno, Uichi Koshimizu, Shinsuke Yuasa, Satoshi Ogawa, Shinya Yamanaka, Kenji Yasuda, Keiichi Fukuda

Research output: Contribution to journalArticle

167 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)497-502
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume385
Issue number4
DOIs
Publication statusPublished - 2009 Aug 7
Externally publishedYes

Fingerprint

Induced Pluripotent Stem Cells
Stem cells
Cardiac Myocytes
Hip
Preclinical Drug Evaluations
Testing
Pharmaceutical Preparations
Screening
Cardiac Electrophysiologic Techniques
Torsades de Pointes
Atrial Natriuretic Factor
Ion Channels
Cardiac Arrhythmias
Assays
Electrodes
In Vitro Techniques

Keywords

  • Arrhythmia
  • Cardiomyocyte
  • Drug screening
  • Human iPS cell
  • Ion channel

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

Cite this

In vitro pharmacologic testing using human induced pluripotent stem cell-derived cardiomyocytes. / Tanaka, Tomofumi; Tohyama, Shugo; Murata, Mitsushige; Nomura, Fumimasa; Kaneko, Tomoyuki; Chen, Hao; Hattori, Fumiyuki; Egashira, Toru; Seki, Tomohisa; Ohno, Yohei; Koshimizu, Uichi; Yuasa, Shinsuke; Ogawa, Satoshi; Yamanaka, Shinya; Yasuda, Kenji; Fukuda, Keiichi.

In: Biochemical and Biophysical Research Communications, Vol. 385, No. 4, 07.08.2009, p. 497-502.

Research output: Contribution to journalArticle

Tanaka, T, Tohyama, S, Murata, M, Nomura, F, Kaneko, T, Chen, H, Hattori, F, Egashira, T, Seki, T, Ohno, Y, Koshimizu, U, Yuasa, S, Ogawa, S, Yamanaka, S, Yasuda, K & Fukuda, K 2009, 'In vitro pharmacologic testing using human induced pluripotent stem cell-derived cardiomyocytes', Biochemical and Biophysical Research Communications, vol. 385, no. 4, pp. 497-502. https://doi.org/10.1016/j.bbrc.2009.05.073
Tanaka, Tomofumi ; Tohyama, Shugo ; Murata, Mitsushige ; Nomura, Fumimasa ; Kaneko, Tomoyuki ; Chen, Hao ; Hattori, Fumiyuki ; Egashira, Toru ; Seki, Tomohisa ; Ohno, Yohei ; Koshimizu, Uichi ; Yuasa, Shinsuke ; Ogawa, Satoshi ; Yamanaka, Shinya ; Yasuda, Kenji ; Fukuda, Keiichi. / In vitro pharmacologic testing using human induced pluripotent stem cell-derived cardiomyocytes. In: Biochemical and Biophysical Research Communications. 2009 ; Vol. 385, No. 4. pp. 497-502.
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