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

doi:10.1016/j.bbrc.2009.05.073

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 journal › Article › peer-review

191 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 language	English
Pages (from-to)	497-502
Number of pages	6
Journal	Biochemical and Biophysical Research Communications
Volume	385
Issue number	4
DOIs	https://doi.org/10.1016/j.bbrc.2009.05.073
Publication status	Published - 07-08-2009
Externally published	Yes

All Science Journal Classification (ASJC) codes

Biophysics
Biochemistry
Molecular Biology
Cell Biology

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10.1016/j.bbrc.2009.05.073

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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

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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.",

keywords = "Arrhythmia, Cardiomyocyte, Drug screening, Human iPS cell, Ion channel",

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

year = "2009",

month = aug,

day = "7",

doi = "10.1016/j.bbrc.2009.05.073",

language = "English",

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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

TY - JOUR

T1 - In vitro pharmacologic testing using human induced pluripotent stem cell-derived cardiomyocytes

AU - Tanaka, Tomofumi

AU - Tohyama, Shugo

AU - Murata, Mitsushige

AU - Nomura, Fumimasa

AU - Kaneko, Tomoyuki

AU - Chen, Hao

AU - Hattori, Fumiyuki

AU - Egashira, Toru

AU - Seki, Tomohisa

AU - Ohno, Yohei

AU - Koshimizu, Uichi

AU - Yuasa, Shinsuke

AU - Ogawa, Satoshi

AU - Yamanaka, Shinya

AU - Yasuda, Kenji

AU - Fukuda, Keiichi

PY - 2009/8/7

Y1 - 2009/8/7

N2 - 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.

AB - 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.

KW - Arrhythmia

KW - Cardiomyocyte

KW - Drug screening

KW - Human iPS cell

KW - Ion channel

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JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

IS - 4

ER -

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

Abstract

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