Noninvasive analysis of contractile function of human iPS-derived cardiomyocytes
Project/Area Number |
17K19499
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Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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Allocation Type | Multi-year Fund |
Research Field |
Pharmaceutical Sciences and related fields
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Research Institution | University of Shizuoka |
Principal Investigator |
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Project Period (FY) |
2017-06-30 – 2020-03-31
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Project Status |
Completed (Fiscal Year 2019)
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Budget Amount *help |
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
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Keywords | 心毒性 / ヒトiPS細胞 / 品質評価 / 薬理学 / 幹細胞 / スクリーニング / 心臓 / 力学的機能 / iPS細胞 / 筋収縮 / 動きベクトル解析 / 組織特異性 |
Outline of Final Research Achievements |
In this study, we aimed to non-invasively identify the tissue-specific properties of human iPS cell-derived cardiomyocytes using motion vector analysis. We demonstrated that commercially available human iPS cell-derived cardiomyocytes have diverse properties by examining the contractile functions of cells that have been dyed by antibody immunostaining against an atrial muscle marker and a ventricular muscle marker. It was found that the contraction speed and relaxation speed of atrial-type was faster than those of ventricular-type. This result was in the same tendency as the difference observed in mouse atrial myocytes and ventricular myocytes, and there was a difference in the reactivity among different class of cardiovascular reagents. From the above, we have developed a novel experimental system that can non-invasively evaluate the drug actions.
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Academic Significance and Societal Importance of the Research Achievements |
本研究成果はヒトiPS細胞由来心筋細胞同株の細胞間における機能的ばらつきを定量的に評価できるようにしたことであり、基礎および応用研究に汎用されるヒトiPS細胞由来分化細胞の品質評価法を確立した点は学術的に意義が高い。 そして、ヒトiPS細胞を用いることで、これまで問題となっていた実験動物とヒトの違いから生じる非臨床試験と臨床でのギャップを埋め、不整脈や心不全などの重篤な副作用(心毒性)を新薬開発の非臨床段階で忌避する技術に応用できることが社会的意義である。
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Report
(4 results)
Research Products
(34 results)
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[Journal Article] Systematic Expression Analysis of Genes Related to Generation of Action Potentials in Human iPS Cell-Derived Cardiomyocytes2019
Author(s)
Masami Kodama, Kazuharu Furutani, Reiko Kimura, Tomoko Ando, Kazuho Sakamoto, Shushi Nagamori, Takashi Ashihara, Yoshihisa Kurachi, Yuko Sekino, Tetsushi Furukawa, Yasunari Kanda, Junko Kurokawa
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Journal Title
Journal of Pharmacological Sciences
Volume: 140
Issue: 4
Pages: 325-330
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Assessment of molecular mechanisms of sex-dependent drug-induced arrhythmias.2019
Author(s)
Kevin R DeMarco, Pei-Chi Yang, Kazuharu Furutani, Branden Brown, John R Dawson, Sergei Y Noskov, Vladimie Yarov-Yarovoy, Jon T Sack, Junko Kurokawa, Heike Wulff, Colleen E Clancy, Igor Vorobyov
Organizer
American Heart Association Scientific Sessions Meeting 2019
Related Report
Int'l Joint Research
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