iPS細胞を用いたSCVTdP疾患概念の構築と新規治療方法の開発

2015 Fiscal Year Annual Research Report

• Project/Area Number: 26670408
• Research Institution: Keio University
• Principal Investigator: 湯浅 慎介 慶應義塾大学, 医学部, 講師 (90398628)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: iPS細胞 / 不整脈

Outline of Annual Research Achievements

Short-coupled variant of torsade de pointes（SCVTdP）は、1994年にLeenhardtらにより報告された、比較的新しい疾患概念である。器質的心臓疾患の無い若年成人が連結器の短い心室性期外収縮に続く多形性心室頻拍を呈し、突然死の高いリスクを有する。その後も症例報告は散発的に認めるが、まとまった報告はなく、患者数、有病率、発症原因等は不明である。しかし高率に心室細動から突然死を認め、予後が悪く厳重な管理が必要であることは認識され、日本循環器病学会ガイドラインにおいて診断基準も提示されているが、疾患原因や治療方法等に関しては全く分かっていない。本研究においては、患者ゲノムに記録された全遺伝情報を保持している患者特異的iPS細胞を用いて、SCVTdPの病態解明、疾患概念確立と治療方法の開発を目的とする。これまでにSCVTdP患者からiPS細胞を作製し、同iPS細胞由来心筋細胞を用いた電気生理学的解析系を構築した。さらに同実験系を用いることによりSCVTdPに特異的な電気生理学的特徴を見出した。

Research Products

• [Journal Article] Glutamine Oxidation Is Indispensable for Survival of Human Pluripotent Stem Cells. (2016)
  • Author(s): Tohyama S, Fujita J, Hishiki T, Matsuura T, Hattori F, Ohno R, Kanazawa H, Seki T, Nakajima K, Kishino Y, Okada M, Hirano A, Kuroda T, Yasuda S, Sato Y, Yuasa S, Sano M, Suematsu M, Fukuda K.
  • Journal Title: Cell Metab Volume: 23 Pages: 663-74
  • DOI: 10.1016/j.cmet.2016.03.001.
  • Peer Reviewed
• [Journal Article] A Novel Wire-Assisted Technique for Closing Large Atrial Septal Defects: New Concepts of Closure Mechanism. (2016)
  • Author(s): Kanazawa H, Kawamura A, Kimura M, Akita K, Yashima F, Arai T, Kawakami T, Hayashida K, Tsuruta H, Yuasa S, Itabashi Y, Murata M, Maekawa Y, Fukuda K.
  • Journal Title: JACC Cardiovasc Interv Volume: 9 Pages: e59-61.
  • DOI: 10.1016/j.jcin.2015.12.016.
  • Peer Reviewed
• [Journal Article] In-Stent Dissection Causes No Flow During Percutaneous Coronary Intervention. (2016)
  • Author(s): Yashima F, Yuasa S, Maekawa Y, Kimura M, Akita K, Yanagisawa R, Tanaka M, Hayashida K, Kawakami T, Kanazawa H, Fujita J, Fukuda K.
  • Journal Title: JACC Cardiovasc Interv. Volume: 9 Pages: 9
  • DOI: 10.1016/j.jcin.2015.09.025.
  • Peer Reviewed
• [Journal Article] "Moving left ventricular obstruction" due to stress cardiomyopathy in a patient with hypertrophic obstructive cardiomyopathy treated with percutaneous transluminal septal myocardial ablation. (2016)
  • Author(s): Akita K, Maekawa Y, Tsuruta H, Okuda S, Yanagisawa R, Kageyama T, Kawakami T, Kanazawa H, Hayashida K, Yuasa S, Murata M, Jinzaki M, Fukuda K.
  • Journal Title: Int J Cardiol Volume: 202 Pages: 194-5.
  • DOI: 10.1016/j.ijcard.2015.08.145.
  • Peer Reviewed
• [Journal Article] Patient-Specific Induced Pluripotent Stem Cell Models: Characterization of iPS Cell-Derived Cardiomyocytes. (2016)
  • Author(s): Egashira T, Yuasa S, Tohyama S, Kuroda Y, Suzuki T, Seki T, Fukuda K.
  • Journal Title: Methods Mol Biol. Volume: 1353 Pages: 343-53.
  • DOI: 10.1007/7651_2014_165.
  • Peer Reviewed
• [Journal Article] Generation of Induced Pluripotent Stem Cells from Human Peripheral T Cells Using Sendai Virus in Feeder-free Conditions. (2015)
  • Author(s): Kishino Y, Seki T, Yuasa S, Fujita J, Fukuda K.
  • Journal Title: J Vis Exp Volume: 105 Pages: 105
  • DOI: 10.3791/53225.
  • Peer Reviewed
• [Journal Article] "Protruding Myocardium" as a Target for Percutaneous Transluminal Septal Myocardial Ablation in a Case of Hypertrophic Obstructive Cardiomyopathy. (2015)
  • Author(s): Maekawa Y, Akita K, Tsuruta H, Yashima F, Kimura M, Yamada Y, Kawakami T, Kanazawa H, Hayashida K, Yuasa S, Murata M, Jinzaki M, Fukuda K.
  • Journal Title: JACC Cardiovasc Interv. Volume: 8 Pages: e201-2.
  • DOI: 10.1016/j.jcin.2015.05.029.
  • Peer Reviewed
• [Journal Article] Cardiovascular Disease Modeling Using Patient-Specific Induced Pluripotent Stem Cells. (2015)
  • Author(s): Tanaka A, Yuasa S, Node K, Fukuda K.
  • Journal Title: Int J Mol Sci. Volume: 16 Pages: 18894-922.
  • DOI: 10.3390/ijms160818894.
  • Peer Reviewed
• [Journal Article] Analysis of cardiomyocyte movement in the developing murine heart. (2015)
  • Author(s): Hashimoto H, Yuasa S, Tabata H, Tohyama S, Seki T, Egashira T, Hayashiji N, Hattori F, Kusumoto D, Kunitomi A, Takei M, Kashimura S, Yozu G, Shimojima M, Motoda C, Muraoka N, Nakajima K, Sakaue-Sawano A, Miyawaki A, Fukuda K.
  • Journal Title: Biochem Biophys Res Commun. Volume: 464 Pages: 1000-7.
  • DOI: 10.1016/j.bbrc.2015.07.036.
  • Peer Reviewed
• [Journal Article] The Role of Circadian Rhythms in Fatal Arrhythmias and the Potential Impact of Intervention for Sleep-Disordered Breathing. (2015)
  • Author(s): Aizawa Y, Kohno T, Yuasa S, Fukuda K.
  • Journal Title: Curr Pharm Des. Volume: 21 Pages: 3512-22.
  • Peer Reviewed
• [Journal Article] G-CSF supports long-term muscle regeneration in mouse models of muscular dystrophy. (2015)
  • Author(s): Hayashiji N, Yuasa S, Miyagoe-Suzuki Y, Hara M, Ito N, Hashimoto H, Kusumoto D, Seki T, Tohyama S, Kodaira M, Kunitomi A, Kashimura S, Takei M, Saito Y, Okata S, Egashira T, Endo J, Sasaoka T, Takeda S, Fukuda K.
  • Journal Title: Nat Commun. Volume: 6 Pages: 6745
  • DOI: 10.1038/ncomms7745.
  • Peer Reviewed
• [Journal Article] Lesion morphological classification by OCT to predict therapeutic efficacy after balloon pulmonary angioplasty in CTEPH. (2015)
  • Author(s): Inohara T, Kawakami T, Kataoka M, Yamamoto M, Kimura M, Kanazawa H, Yuasa S, Hayashida K, Maekawa Y, Fukuda K.
  • Journal Title: Lesion morphological classification by OCT to predict therapeutic efficacy after balloon pulmonary angioplasty in CTEPH. Volume: 197 Pages: 2015
  • DOI: 10.1016/j.ijcard.2015.06.036.
  • Peer Reviewed