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

170 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

Keywords

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

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'In vitro pharmacologic testing using human induced pluripotent stem cell-derived cardiomyocytes'. Together they form a unique fingerprint.

  • Cite this

    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, 385(4), 497-502. https://doi.org/10.1016/j.bbrc.2009.05.073