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Production of Subtype Specific Cardiomyocytes from Human iPSCs Based on Metabolism

Research Project

Project/Area Number 17H05067
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypeSingle-year Grants
Research Field General medical chemistry
Research InstitutionKeio University

Principal Investigator

TOHYAMA Shugo  慶應義塾大学, 医学部(信濃町), 特任講師 (90528192)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥24,310,000 (Direct Cost: ¥18,700,000、Indirect Cost: ¥5,610,000)
Fiscal Year 2019: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
Fiscal Year 2018: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
Fiscal Year 2017: ¥9,490,000 (Direct Cost: ¥7,300,000、Indirect Cost: ¥2,190,000)
KeywordsヒトiPS細胞 / 代謝 / 心筋細胞 / 移植 / 創薬 / 幹細胞生物学 / 再生医療 / iPS細胞 / 再生医学 / 細胞移植
Outline of Final Research Achievements

The purpose of this study is to develop an efficient method to produce subtype specific cardiomyocytes from human iPSCs via metabolic regulation for regenerative medicine and drug discovery. In this project, we identified optimal culture conditions for human iPSCs expansion (1). In addition, we also developed an efficient method to produce subtype specific cardiomyocytes from human iPSCs (2). Moreover, we evaluated metabolic profiles in subtype specific cardiomyocytes via multi-omics (3). These findings will eventually promote the clinical applications of regenerative medicine and drug discovery.

Academic Significance and Societal Importance of the Research Achievements

本研究成果の学術的意義は、代謝プロファイルを基盤にヒトiPS細胞の増殖能をコントロールするだけでなく、高純度心室筋細胞と非心室筋細胞を作り分ける技術を開発することで、表現型のばらつきを解消する点である。表現型のばらつきを解消することで、安全かつ有効な再生医療の実現化および創薬への応用が期待できるため、社会的意義も極めて高いと考えられる。

Report

(3 results)
  • 2019 Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (17 results)

All 2019 2018 2017

All Journal Article (4 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 4 results,  Open Access: 1 results) Presentation (13 results) (of which Int'l Joint Research: 5 results,  Invited: 9 results)

  • [Journal Article] Development of a transplant injection device for optimal distribution and retention of human induced pluripotent stem cell-derived cardiomyocytes2019

    • Author(s)
      Tabei R, Kawaguchi S, Kanazawa H, Tohyama S, Hirano A, Handa N, Hishikawa S, Teratani T, Kunita S, Fukuda J, Mugishima Y, Suzuki T, Nakajima K, Seki T, Kishino Y, Okada M, Yamazaki M, Okamoto K, Shimizu H, Kobayashi E, Tabata Y, Fujita J, Fukuda K
    • Journal Title

      The Journal of heart and lung transplantation

      Volume: 38 Issue: 2 Pages: 203-214

    • DOI

      10.1016/j.healun.2018.11.002

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Selective elimination of undifferentiated human pluripotent stem cells using pluripotent state-specific immunogenic antigen Glypican-3.2019

    • Author(s)
      Okada M, Tada Y, Seki T, Tohyama S, Fujita J, Suzuki T, Shimomura M, Ofuji K, Kishino Y, Nakajima K, Tanosaki S, Someya S, Kanazawa H, Senju S, Nakatsura T, Fukuda K.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 511 Issue: 3 Pages: 711-717

    • DOI

      10.1016/j.bbrc.2019.02.094

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Efficient large-scale 2D culture system for human induced pluripotent stem cells and differentiated cardiomyocytes.2017

    • Author(s)
      Toyama S, Fujita J*, Fujita C, Yamaguchi M, Kanaami S, Ohno R, Sakamoto K, Kodama M, Kurokawa J, Kanazawa H, Seki T, Kishino Y, Okada M, Nakajima K, Tanosaki S, Someya S, Hirano A, Kawaguchi S, Kobayashi E, Fukuda K
    • Journal Title

      Stem Cell Rep

      Volume: 9 Issue: 5 Pages: 1406-1414

    • DOI

      10.1016/j.stemcr.2017.08.025

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Safe and Effective Cardiac Regenerative Therapy With Human-Induced Pluripotent Stem Cells: How Should We Prepare Pure Cardiac Myocytes?2017

    • Author(s)
      Tohyama S, Fukuda K
    • Journal Title

      Circulation research

      Volume: 120(10) Issue: 10 Pages: 1558-1560

    • DOI

      10.1161/circresaha.116.310328

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] ヒトiPS細胞を用いた心臓再生医療実現化に向けた取り組み2019

    • Author(s)
      遠山周吾
    • Organizer
      第18回日本再生医療学会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] ヒトiPS細胞由来心筋細胞を用いた創薬および再生医療の具現化における課題と対策2019

    • Author(s)
      遠山周吾
    • Organizer
      第6回心臓安全性に関するシンクタンクミーティング2019合同公開シンポジウム
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] ヒトiPS細胞が拓く心臓再生医療の未来2018

    • Author(s)
      遠山周吾
    • Organizer
      第22回日本心不全学会学術集会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 代謝制御によるヒトiPS細胞由来心筋細胞の大量作製とその応用2018

    • Author(s)
      遠山周吾
    • Organizer
      第91回日本生化学会大会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Safe and Effective Cardiac Regenerative Medicine with Human iPSCs2018

    • Author(s)
      遠山周吾
    • Organizer
      第2回日本循環器学会基礎研究フォーラム
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Development of a Massive Cardiac Spheroids Production and Transplantation System in Human Pluripotent Stem Cells2018

    • Author(s)
      Shugo Tohyama
    • Organizer
      he 16th annual scientific meeting of the International Society for Stem Cell Research (ISSCR) 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ヒト多能性幹細胞における代謝機構の理解と心臓再生医療への応用2018

    • Author(s)
      遠山周吾
    • Organizer
      第43回日本微小循環学会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Metabolic Selection System for Large Numbers of Human iPSC-Derived Cardiomyocytes2018

    • Author(s)
      Shugo Tohyama
    • Organizer
      Weinstein 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] バイオ3Dプリンタを用いたヒトiPS細胞由来心筋組織構造体の作製2018

    • Author(s)
      遠山周吾、荒井健一、川口新治、木村成卓、藤田淳、福田恵一、中山功一、小林英司
    • Organizer
      日本再生医療学会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Efficient Large-Scale 2D Culture System for Human iPSCs and Differentiated Cardiomyocytes2017

    • Author(s)
      Shugo Tohyama, Jun Fujita, Chihana Fujita, Sayaka Kanaami, Rei Ohno, Keiichi Fukuda
    • Organizer
      CiRA international symposium
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Efficient Large-Scale 2D Culture System for Human Pluripotent Stem Cells and Differentiated Cardiomyocytes2017

    • Author(s)
      Shugo Tohyama, Jun Fujita, Chihana Fujita, Sayaka Kanaami, Rei Ohno, Keiichi Fukuda
    • Organizer
      The 15th annual scientific meeting of the International Society for Stem Cell Research (ISSCR) 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Manipulation of Pluripotent Stem Cell Metabolism for Cardiac Regenerative Medicine2017

    • Author(s)
      Shugo Tohyama
    • Organizer
      The 47th Annual Scientific Meeting of the Taiwan Society of Cardiology
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] ヒト多能性幹細胞における代謝制御と心臓再生医療への応用2017

    • Author(s)
      遠山 周吾
    • Organizer
      第53回日本小児循環器学会
    • Related Report
      2017 Annual Research Report
    • Invited

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Published: 2017-04-28   Modified: 2021-02-19  

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