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Mechanism of cardiac reprogramming associated with aging

Research Project

Project/Area Number 19K22613
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 53:Organ-based internal medicine and related fields
Research InstitutionUniversity of Tsukuba

Principal Investigator

Ieda Masaki  筑波大学, 医学医療系, 教授 (70296557)

Project Period (FY) 2019-06-28 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2020: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2019: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywords心臓再生 / 心筋リプログラミング / 再生 / 化合物 / リプログラミング
Outline of Research at the Start

これまで加齢に伴う心筋リプログラミング抵抗性の分子機序を明らかにした報告は皆無であり、本研究は独創性・新規性の高い基礎研究であるだけでなく、心臓再生治療への応用という点で臨床的にも重要な研究である。我々はこれまで世界に先駆けて線維芽細胞の心筋リプログラミングに成功し、さらに加齢に伴う心筋リプログラミング抵抗性という現象を見出している。本研究はこれまで自らが積み上げてきた心筋リプログラミング研究の多くの知見や材料を利用するため、他より圧倒的に優位な立場で研究を進められる。また本研究成果は加齢に伴う線維化亢進の分子機構や抗線維化治療など他臓器にも一般化できる内容であり、大きな波及効果を期待できる。

Outline of Final Research Achievements

Cardiac disease is increasing with aging, and the development of a heart regeneration method is required as a new treatment. Therefore, in this study, chemical screening was performed to determine the molecular mechanism of age-related myocardial reprogramming resistance and new compounds that can improve it. This will enable the establishment of a safe and efficient myocardial reprogramming method, which will greatly advance the realization of cardiac regenerative medicine.

Academic Significance and Societal Importance of the Research Achievements

これまで加齢に伴う心筋リプログラミング抵抗性の分子機序を明らかにした報告は皆無であり、本研究は独創性・新規性の高い基礎研究であるだけでなく、心臓再生治療への応用という点で臨床的にも重要な研究である。我々はこれまで世界に先駆けて線維芽細胞の心筋リプログラミングに成功し、さらに加齢に伴う心筋リプログラミング抵抗性という現象を見出している。本研究はこれまで自らが積み上げてきた心筋リプログラミング研究の多くの知見や材料を利用するため、他より圧倒的に優位な立場で研究を進められる。また本研究成果は加齢に伴う線維化亢進の分子機構や抗線維化治療など他臓器にも一般化できる内容であり、大きな波及効果を期待できる。

Report

(5 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (30 results)

All 2023 2022 2021 2020 2019

All Journal Article (10 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 10 results,  Open Access: 8 results) Presentation (18 results) (of which Int'l Joint Research: 9 results,  Invited: 18 results) Book (2 results)

  • [Journal Article] Development of direct cardiac reprogramming for clinical applications2023

    • Author(s)
      Yamada Yu、Sadahiro Taketaro、Ieda Masaki
    • Journal Title

      Journal of Molecular and Cellular Cardiology

      Volume: 178 Pages: 1-8

    • DOI

      10.1016/j.yjmcc.2023.03.002

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Direct Reprogramming Improves Cardiac Function and Reverses Fibrosis in Chronic Myocardial Infarction2023

    • Author(s)
      Tani Hidenori、Sadahiro Taketaro、Yamada Yu、Isomi Mari、Yamakawa Hiroyuki、Fujita Ryo、Abe Yuto、Akiyama Tatsuya、Nakano Koji、Kuze Yuta、Seki Masahide、Suzuki Yutaka、Fujisawa Manabu、Sakata-Yanagimoto Mamiko、Chiba Shigeru、Fukuda Keiichi、Ieda Masaki
    • Journal Title

      Circulation

      Volume: 147 Issue: 3 Pages: 223-238

    • DOI

      10.1161/circulationaha.121.058655

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A biomimetic hydrogel culture system to facilitate cardiac reprogramming2022

    • Author(s)
      Kurotsu Shota、Sadahiro Taketaro、Harada Ichiro、Ieda Masaki
    • Journal Title

      STAR Protocols

      Volume: 3 Issue: 1 Pages: 101122-101122

    • DOI

      10.1016/j.xpro.2022.101122

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] In vivo reprogramming as a new approach to cardiac regenerative therapy2022

    • Author(s)
      Sadahiro Taketaro、Ieda Masaki
    • Journal Title

      Seminars in Cell & Developmental Biology

      Volume: 122 Pages: 21-27

    • DOI

      10.1016/j.semcdb.2021.06.019

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Overexpression of Gata4, Mef2c, and Tbx5 Generates Induced Cardiomyocytes Via Direct Reprogramming and Rare Fusion in the Heart2021

    • Author(s)
      Isomi Mari、Sadahiro Taketaro、Yamakawa Hiroyuki、Fujita Ryo、Yamada Yu、Abe Yuto、Murakata Yoshiko、Akiyama Tatsuya、Shu Tsugumine、Mizukami Hiroaki、Fukuda Keiichi、Ieda Masaki
    • Journal Title

      Circulation

      Volume: 143 Issue: 21 Pages: 2123-2125

    • DOI

      10.1161/circulationaha.120.052799

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Direct reprogramming with Sendai virus vectors repaired infarct hearts at the chronic stage2021

    • Author(s)
      Isomi Mari、Sadahiro Taketaro、Fujita Ryo、Abe Yuto、Yamada Yu、Akiyama Tatsuya、Mizukami Hiroaki、Shu Tsugumine、Fukuda Keiichi、Ieda Masaki
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 560 Pages: 87-92

    • DOI

      10.1016/j.bbrc.2021.04.121

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Soft Matrix Promotes Cardiac Reprogramming via Inhibition of YAP/TAZ and Suppression of Fibroblast Signatures2020

    • Author(s)
      Kurotsu Shota、Sadahiro Taketaro、Fujita Ryo、Tani Hidenori、Yamakawa Hiroyuki、Tamura Fumiya、Isomi Mari、Kojima Hidenori、Yamada Yu、Abe Yuto、Murakata Yoshiko、Akiyama Tatsuya、Muraoka Naoto、Harada Ichiro、Suzuki Takeshi、Fukuda Keiichi、Ieda Masaki
    • Journal Title

      Stem Cell Reports

      Volume: 15 Issue: 3 Pages: 612-628

    • DOI

      10.1016/j.stemcr.2020.07.022

    • NAID

      120007165453

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Key Regulators of Cardiovascular Differentiation and Regeneration: Harnessing the Potential of Direct Reprogramming to Treat Heart Failure2020

    • Author(s)
      IEDA MASAKI
    • Journal Title

      Journal of Cardiac Failure

      Volume: 26 Issue: 1 Pages: 80-84

    • DOI

      10.1016/j.cardfail.2019.09.005

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Direct Cardiac Reprogramming for Cardiovascular Regeneration and Differentiation2019

    • Author(s)
      Sadahiro Taketaro、Ieda Masaki
    • Journal Title

      The Keio Journal of Medicine

      Volume: - Issue: 3 Pages: 49-58

    • DOI

      10.2302/kjm.2019-0008-oa

    • NAID

      130007907362

    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 2.Tbx6 induces cardiomyocyte proliferation in postnatal and adult mouse hearts.2019

    • Author(s)
      Haginiwa S, Sadahiro T, Kojima H, Isomi M, Tamura F, Kurotsu S, Tani H, Muraoka N, Miyake N, Miyake K, Fukuda K, Ieda M.
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 513 Issue: 4 Pages: 1041-1047

    • DOI

      10.1016/j.bbrc.2019.04.087

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Application of direct reprogramming technology into cardiomyocyte regeneration2023

    • Author(s)
      家田真樹
    • Organizer
      第22回日本再生医療学会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] Direct Reprogramming for Cardiac Regeneration2022

    • Author(s)
      Masaki Ieda
    • Organizer
      The 16th Oriental Congress of Cardiology OCC-JCS Joint session
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] ダイレクトリプログラミングによる心臓再生遺伝子治療2022

    • Author(s)
      家田真樹
    • Organizer
      第70回日本心臓病学会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 心臓線維化と心筋再生2022

    • Author(s)
      家田真樹
    • Organizer
      第26回日本心不全学会学術集会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] Cardiac Fibrosis, Reprogramming, and Regeneration2022

    • Author(s)
      家田真樹
    • Organizer
      第86 回日本循環器学会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] ダイレクトリプログラミングによる新しい心臓再生法の開発2022

    • Author(s)
      家田真樹
    • Organizer
      武蔵野大学・人間科学研究所シンポジウム
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] Cardiac reprogramming and regeneration2021

    • Author(s)
      Masaki Ieda
    • Organizer
      5th International Forum on Medical Innovation of Cell & Bio Therapy
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Converting scar tissue to heart muscle after a heart attack2021

    • Author(s)
      Masaki Ieda
    • Organizer
      2021 Annual Spring Scientific Conference of the Korean Society of Cardiology
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 心臓再生医療の現状と展望 ダイレクトリプログラミングによる心臓再生2021

    • Author(s)
      家田真樹
    • Organizer
      第25回日本心不全学会学術集会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] YAP/TAZ and Fibrosis: New Link between Cardiac Reprogramming and Mechanobiology2021

    • Author(s)
      家田真樹
    • Organizer
      第85回日本循環器学会学術集会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] ダイレクトリプログラミングを用いた心筋再生2021

    • Author(s)
      家田真樹
    • Organizer
      第20回日本再生医療学会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] Direct reprogramming for Cardiac Regeneration2020

    • Author(s)
      Masaki Ieda
    • Organizer
      ISHR Asia-Pacific Cardiovascular Webinar
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] DIRECT REPROGRAMMING INTO CARDIOVASCULAR LINEAGES2020

    • Author(s)
      Masaki Ieda
    • Organizer
      ISSCR 2020 annual web meeting
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 心筋リプログラミング研究の新しい展開2020

    • Author(s)
      家田真樹
    • Organizer
      第24回日本心不全学会学術集会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] Making New Muscle Cells from Fibroblasts for Heart Regeneration2019

    • Author(s)
      Masaki Ieda
    • Organizer
      The KAST-NAMOK joint International Symposium
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Direct Reprogramming for Cardiovascular Regeneration2019

    • Author(s)
      Masaki Ieda
    • Organizer
      CSSCR annual session
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Direct reprogramming and cardiovascular research2019

    • Author(s)
      Masaki Ieda
    • Organizer
      AHA BCVS 2019 Scientific Sessions Symposium
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Direct Reprogramming toward Cutting-edge Cardiovascular Research2019

    • Author(s)
      Masaki Ieda
    • Organizer
      Gwangju-International Interventioanl Cardiology Symposium
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Book] 新たな心筋再生技術―ダイレクトリプログラミング2022

    • Author(s)
      村岡直人、家田真樹
    • Total Pages
      6
    • Publisher
      医学のあゆみ
    • Related Report
      2022 Annual Research Report
  • [Book] 心血管発生と再生医学への新しい展開2022

    • Author(s)
      貞廣威太郎, 家田真樹
    • Total Pages
      5
    • Publisher
      科学評論社
    • Related Report
      2022 Annual Research Report

URL: 

Published: 2019-07-04   Modified: 2024-01-30  

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