Development of mature cardiomyocytes from human iPS cells
| Project/Area Number |
26293056
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
General pharmacology
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| Research Institution | National Institute of Health Sciences |
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Principal Investigator |
Kanda Yasunari 国立医薬品食品衛生研究所, 薬理部, 室長 (70510387)
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| Co-Investigator(Kenkyū-buntansha) |
大島 英揮 名古屋大学, 医学部附属病院, 講師 (40378188)
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| Co-Investigator(Renkei-kenkyūsha) |
Kurokawa Junko 静岡県立大学, 薬学部, 教授 (40396982)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥16,120,000 (Direct Cost: ¥12,400,000、Indirect Cost: ¥3,720,000)
Fiscal Year 2016: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2015: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
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| Keywords | iPS細胞 / 心筋細胞 / 成熟化 / インシリコ / イオンチャネル / 安全性薬理 / 不整脈 / 安全性評価 / 創薬 / ヒトiPS細胞 / 多点電極 / 興奮伝播 / 液性因子 / 心筋 / 幹細胞 / 再生医療 |
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| Outline of Final Research Achievements |
Drug-induced cardiac arrhythmias have been a major reason for drug withdrawal at late stage of clinical trials. Human induced pluripotent stem cell-derived cardiomyocytes (iPS-CMs) are expected to be applicable to cardiac drug safety testing as research tools. In the present study, our patch-clamp recordings and imaging with voltage-sensitive dye revealed that iPS-CMs exhibited relatively depolarized maximum diastolic potential and lower conduction velocity, suggesting an immature differentiation state of the iPS-CMs. We next established our mathematical simulation in iPS-CMs and found that low expression of the inward-rectifier potassium (IK1) channel is a determinant of spontaneous activity. We also fond that transduction of KCNJ2, which encodes the IK1 channel, induced electrophysiological maturation of iPS-CMs. Thus, our novel approach would provide new insights into the evaluation of drug-induced caridiac toxicities in iPS-CMs.
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Report
(4 results)
Research Products
(47 results)
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[Journal Article] A new paradigm for drug-induced torsadogenic risk assessment using human iPS cell-derived cardiomyocytes.2017
Author(s)
Ando H, Yoshinaga T, Yamamoto W, Asakura K, Uda T, Taniguchi T, Ojima A, Shinkyo R, Kikuchi K, Osada T, Hayashi S, Kasai C, Miyamoto N, Tashibu H, Yamazaki D, Sugiyama A, Kanda Y, Sawada K, Sekino Y.
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Journal Title
J Pharmacol Toxicol Methods
Volume: 84
Pages: 111-127
Related Report
Peer Reviewed / Open Access
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[Journal Article] Good Cell Culture Practice for stem cells and stem-cell-derived models.2016
Author(s)
Pamies D, Bal-Price A, Simeonov A, Tagle D, Allen D, Gerhold D, Yin D, Pistollato F, Inutsuka T, Sullivan K, Stacey G, Salem H, Leist M, Daneshian M, Vemuri MC, McFarland R, Coecke S, Fitzpatrick SC, Lakshmipathy U, Mack A, Wang WB, Yamazaki D, Sekino Y, Kanda Y, Smirnova L, Hartung T.
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Journal Title
ALTEX
Volume: 34
Pages: 95-132
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Electrophysiological Characteristics of Human iPSC-Derived Cardiomyocytes for the Assessment of Drug-Induced Proarrhythmic Potential.2016
Author(s)
Yamamoto W, Asakura K, Ando H, Taniguchi T, Ojima A, Uda T, Osada T, Hayashi S, Kasai C, Miyamoto N, Tashibu H, Yoshinaga T, Yamazaki D, Sugiyama A, Kanda Y, Sawada K, Sekino Y.
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Journal Title
Related Report
Peer Reviewed / Open Access
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[Presentation] Electrophysiological and Pharmacological Characterization of Human iPS Cell-Derived Cardiomyocytes As a Model for Predicting the Drug-Induced Arrhythmic Events in Human Hearts2016
Author(s)
Wataru Yamamoto, Keiichi Asakura, Hiroyuki Ando, Tomohiko Taniguchi, Atsuko Ojima, Takaaki Uda, Tomoharu Osada, Seiji Hayashi, Chieko Kasai, Norimasa Miyamoto, Hiroyuki Tashibu, Takashi Yoshinaga, Daiju Yamazaki, Atsushi Sugiyama, Yasunari Kanda, Kohei Sawada, Yuko Sekino
Organizer
Safety Pharmacology Society 16th annual meeting
Place of Presentation
Vancouver, Canada
Year and Date
2016-09-18
Related Report
Int'l Joint Research
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[Presentation] Drug-Induced Torsadogenic Risk Prediction Using Human iPS Cell-Derived Cardiomyocytes and MEA System (I)2016
Author(s)
Hiroyuki Ando, Takashi Yoshinaga, Wataru Yamamoto, Keiichi Asakura, Tomohiko Taniguchi, Atsuko Ojima, Takaaki Uda, Raku Shinkyo, Kiyomi Kikuchi, Tomoharu Osada, Seiji Hayashi, Chieko Kasai, Norimasa Miyamoto, Hiroyuki Tashibu, Daiju Yamazaki, Atsushi Sugiyama, Yasunari Kanda, Kohei Sawada, Yuko Sekino,
Organizer
Safety Pharmacology Society 16th annual meeting
Place of Presentation
Vancouver, Canada
Year and Date
2016-09-18
Related Report
Int'l Joint Research
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[Presentation] Drug-Induced Torsadogenic Risk Prediction Using Human iPS Cell-Derived Cardiomyocytes and MEA System (II)2016
Author(s)
Takashi Yoshinaga, Hiroyuki Ando, Tomohiko Taniguchi, Takaaki Uda, Wataru Yamamoto, Keiichi Asakura, Atsuko Ojima, Raku Shinkyo, Kiyomi Kikuchi, Tomoharu Osada, Seiji Hayashi, Chieko Kasai, Hiroyuki Tashibu, Norimasa Miyamoto, Daiju Yamazaki, Yasunari Kanda, Atsushi Sugiyama, Kohei Sawada, Yuko Sekino,
Organizer
Safety Pharmacology Society 16th annual meeting
Place of Presentation
Vancouver, Canada
Year and Date
2016-09-18
Related Report
Int'l Joint Research
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[Presentation] Evaluation of Multi-electrode Array in Combination with Cor.4U Human iPS Cell-Derived Cardiomyocytes to Predict Drug-Induced QT Prolongation and Arrhythmia -Collaboration between CSAHi and JiCSA2016
Author(s)
Takashi Kitaguchi, Yuta Moriyama, Sanae Maeda, Tomohiko Taniguchi, Masakazu Ishimura, Hiroyuki Tashibu, Masao Oguchi, Atsuhiro Yamanishi, Etsushi Takahashi, Kaori Miyamoto, Kaoru Morimura, Daisuke Saji, Hiroki Ohnaka, Daiju Yamazaki, Yasunari Kanda, Yuko Sekino, Norimasa Miyamoto
Organizer
Safety Pharmacology Society 16th annual meeting
Place of Presentation
Vancouver, Canada
Year and Date
2016-09-18
Related Report
Int'l Joint Research
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[Presentation] A novel approach for evaluation of drug-induced QT prolongation using human induced pluripotent stem cell-derived cardiomyocytes2015
Author(s)
Junko Kurokawa, Jun-ichi Okada, Erina Hayashi, Takashi Ashihara, Takashi Yoshinaga, Seiryo Sugiura, Li Min, Yasunari Kanda, Yuko Sekino, Kohei Sawada, Toshiaki Hisada, Tetsushi Furukawa
Organizer
59th Biophysics meeting
Place of Presentation
Baltimore
Year and Date
2015-02-19
Related Report
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