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Direct reprogramming of human fibroblasts into cardiomyocyte-like cells

Research Project

Project/Area Number 23659426
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Circulatory organs internal medicine
Research InstitutionKeio University

Principal Investigator

IEDA Masaki  慶應義塾大学, 医学部, 特任講師 (70296557)

Project Period (FY) 2011 – 2012
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords心臓 / 再生 / 循環器内科 / リプログラミング / 循環器・高血圧
Research Abstract

Direct reprogramming of differentiated human somatic cells into cardiac cells holds great promise for regenerative medicine. It has not been whether human fibroblasts can be directly reprogrammed into differentiated cardiomyocytes by defined factors. Here, we demonstrate that Gata4, Mef2c, and Tbx5 could also convert postnatal human cardiac fibroblasts directly into cardiomyocyte-like cells, when combined with two additional cardiac transcriptional regulators. Human induced cardiac cells expressed multiple cardiac-specific markers, changed a global gene expression profile toward a cardiomyocyte-like state, and generated spontaneous Ca transients. Importantly, a subset of induced cardiac cells matured to exhibit action potentials and contracted synchronously when co-cultured with primary murine cardiomyocytes. Thus, human fibroblasts can be converted into cardiomyocyte-like cells and these methods may facilitate future applications in regenerative purposes.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (38 results)

All 2014 2013 2012 2011 Other

All Journal Article (12 results) (of which Peer Reviewed: 12 results) Presentation (17 results) (of which Invited: 9 results) Book (8 results) Remarks (1 results)

  • [Journal Article] Endogenous Prostaglandin D2 and Its Metabolites Protect the Heart Against Ischemia-Reperfusion Injury by Activating Nrf22014

    • Author(s)
      Katsumata Y, Shinmura K, Sugiura Y, Tohyama S, Matsuhashi T, Ito H, Yan X, Ito K, Yuasa S, Ieda M, Urade Y, Suematsu M, Fukuda K, Sano M
    • Journal Title

      Hypertension

      Volume: 2013 Issue: 1 Pages: 21-37

    • DOI

      10.1161/hypertensionaha.113.01639

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Induction of Human Cardiomyocyte-like Cells from Fibroblasts by Defined Factors.2013

    • Author(s)
      Wada R, Muraoka N, Inagawa K, Tohyama S, et al
    • Journal Title

      Proc Natl Acad Sci U S A.

      Volume: 110 Issue: 31 Pages: 12667-72

    • DOI

      10.1073/pnas.1304053110

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Srivastava D. Reprogramming of mouse fibroblasts into cardiomyocyte-like cells in vitro2013

    • Author(s)
      Qian L, Berry EC, Fu JD, Ieda M
    • Journal Title

      Nat Protocol

      Volume: 8(6) Issue: 6 Pages: 1204-15

    • DOI

      10.1038/nprot.2013.067

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Direct Cardiac Reprogramming by Defined Factors.2013

    • Author(s)
      Ieda M
    • Journal Title

      Inflammation and Regeneration

      Volume: 33 Pages: 190-196

    • NAID

      130004482307

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Heart Development and Regeneration via Cellular Interaction and Reprogramming.2013

    • Author(s)
      Ieda M.
    • Journal Title

      Keio J

      Volume: 62 Pages: 99-106

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Heart regeneration using reprogramming technology2013

    • Author(s)
      Ieda M
    • Journal Title

      Proc Jpn Acad Ser B Phys Biol Sci.

      Volume: 89 Pages: 118-128

    • NAID

      130003365109

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Direct Reprogramming of Mouse Fibroblasts into Cardiac Myocytes.2013

    • Author(s)
      Inagawa K. and Ieda M
    • Journal Title

      J Cardiovasc Transl Res.

      Volume: 6 Issue: 1 Pages: 37-45

    • DOI

      10.1007/s12265-012-9412-5

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Induction of Cardiomyocyte-like Cells in Infarct Hearts by Gene Transfer of Gata4, Mef2c, and Tbx52012

    • Author(s)
      Inagawa K, Miyamoto K, Yamakawa H, Muraoka N, Sadahiro T, Umei T, Wada R, Katsumata Y, Kaneda R, Nakade K, Kurihara C, Obata Y, Miyake K, Fukuda K, Ieda M
    • Journal Title

      Circulation research

      Volume: 111 Issue: 9 Pages: 1147-56

    • DOI

      10.1161/circresaha.112.271148

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Critical factors for cardiac reprogramming2012

    • Author(s)
      Srivastava, D., and Ieda, M
    • Journal Title

      Circulation research

      Volume: 111 Issue: 1 Pages: 5-8

    • DOI

      10.1161/circresaha.112.271452

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Cardiac repair with thymosin β4 and cardiac reprogramming2012

    • Author(s)
      Srivastava D, Ieda M, Fu J, Qian L.
    • Journal Title

      Ann N Y Acad Sci.

      Volume: 1270 Issue: 1 Pages: 66-72

    • DOI

      10.1111/j.1749-6632.2012.06696.x

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Development, maturation, and transdifferentiation of cardiac sympathetic nerves2012

    • Author(s)
      Kimura K, Ieda M, et al
    • Journal Title

      Circ Res

      Volume: 110 Issue: 2 Pages: 325-336

    • DOI

      10.1161/circresaha.111.257253

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Neural crest-derived stem cells migrate and differentiate into cardiomyocytes after myocardial infarction2011

    • Author(s)
      Yuichi Tamura
    • Journal Title

      Arterioscler. Thromb. Vasc. Biol.

      Volume: 31 Issue: 3 Pages: 582-589

    • DOI

      10.1161/atvbaha.110.214726

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] Bypassing Pluripotency2014

    • Author(s)
      Masaki Ieda
    • Organizer
      19th Medical Research Conference
    • Place of Presentation
      Hong Kong, China
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Direct Reprogramming of Fibroblasts into Cardiomyocyte-like Cells in Infarct Hearts2013

    • Author(s)
      Masaki Ieda
    • Organizer
      Stem Cell and Regenerative Medicine Global Congress 2013
    • Place of Presentation
      Seoul, South Korea
    • Related Report
      2013 Final Research Report 2012 Research-status Report
  • [Presentation] 第77回日本循環器学会学術集会 プレナリーセッション2013

    • Author(s)
      Masaki Ieda
    • Organizer
      Direct Conversion of Fibroblasts into Cardiomyocyte-like Cells by Defined Factors
    • Place of Presentation
      横浜
    • Related Report
      2013 Final Research Report
  • [Presentation] Direct Cardiac Reprogramming by Defined Factors2013

    • Author(s)
      Masaki Ieda
    • Organizer
      International Society for Heart Research (ISHR)
    • Place of Presentation
      San Diego, USA
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Induction of Cardiomyocyte-like Cells by Defined Factors2013

    • Author(s)
      Masaki Ieda
    • Organizer
      American Heart Association Basic Cardiovascular Sciences 2013
    • Place of Presentation
      Las Vegas, Nevada, USA
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Discovery, Progress, and Challenges of Direct Cardiac Reprogramming for Heart Regeneration2013

    • Author(s)
      Masaki Ieda
    • Organizer
      New Jersey Medical School Seminar
    • Place of Presentation
      Newark, NJ, USA
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Induction of Cardiomyocyte-like Cells in Infarct Hearts2013

    • Author(s)
      Masaki Ieda
    • Organizer
      American Heart Association Scientific Sessions 2013
    • Place of Presentation
      Dallas, USA
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 第48回日本小児循環器学会会長特別企画 世紀の発見が医療を変える2012

    • Author(s)
      家田真樹
    • Organizer
      直接リプログラミングによる心筋細胞の作製
    • Place of Presentation
      京都
    • Year and Date
      2012-07-05
    • Related Report
      2013 Final Research Report
  • [Presentation] Conversion of Fibroblasts into Cardiomyocytes by Defined Factors2012

    • Author(s)
      Ieda, M
    • Organizer
      Innovative Research Institute for Cell Therapy Spring Symposium
    • Place of Presentation
      Seoul, South Korea
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] Induction of Cardiomyocyte-like Cells by Defined Factors2012

    • Author(s)
      Ieda, M
    • Organizer
      Korean Society for Stem Cell Research (KSSCR)
    • Place of Presentation
      Seoul, South Korea
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] Induction of Cardiomyocyte-like Cells in vitro and vivo by Defined Factors2012

    • Author(s)
      Ieda, M
    • Organizer
      Heidelberg University Seminar
    • Place of Presentation
      Heidelberg, Germany
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] Reprogramming of Fibroblasts in Infarct Hearts into Cardiomyocyte-like Cells by Defined Factors2012

    • Author(s)
      Ieda, M
    • Organizer
      Oulu Center for Cell-Matrix Research
    • Place of Presentation
      Oulu, Finland
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] Pluripotent Stem Cell Biology, "Direct Reprogramming of Fibroblasts into Functional Cardiomyocytes"2011

    • Author(s)
      Masaki Ieda
    • Organizer
      American Heart Association Scientific Sessions 2011
    • Place of Presentation
      Orlando, Florida, USA
    • Related Report
      2013 Final Research Report
  • [Presentation] A new method for cardiac regeneration -Direct conversion of fibroblasts into cardiomyocytes by defined factors-2011

    • Author(s)
      Masaki Ieda
    • Organizer
      Cologne Conference on Cardiac Regeneration and Cell Therapy 2011 (招待講演)
    • Place of Presentation
      Cologne, Germany
    • Related Report
      2011 Research-status Report
  • [Presentation] Direct reprogramming of fibroblasts to cardiomyocytes2011

    • Author(s)
      Masaki Ieda
    • Organizer
      The Collagen Gordon Conference(招待講演)
    • Place of Presentation
      New London, NH, USA
    • Related Report
      2011 Research-status Report
  • [Presentation] Direct Reprogramming of Fibroblasts into Cardiomyocytes by Defined Factors2011

    • Author(s)
      Masaki Ieda
    • Organizer
      7th International Congress on Stem Cell Biology and Technology(招待講演)
    • Place of Presentation
      Tehran, Iran
    • Related Report
      2011 Research-status Report
  • [Presentation] Direct Reprogramming of Fibroblasts into Functional Cardiomyocytes2011

    • Author(s)
      Masaki Ieda
    • Organizer
      American Heart Association Scientific Sessions 2011(招待講演)
    • Place of Presentation
      Orlando, Florida, USA
    • Related Report
      2011 Research-status Report
  • [Book] Induced Cardiomyocytes : Direct reprogramming for cardiac regeneration "Cardiac Regeneration Using Stem Cells" USA2013

    • Author(s)
      Masaki Ieda
    • Publisher
      CRC Press, Taylor and Francis Group
    • Related Report
      2013 Final Research Report
  • [Book] ダイレクトリプログラミングによる心筋誘導 (2013年8月号, Vol.31, No.13)実験医学2013

    • Author(s)
      貞廣威太郎、家田真樹
    • Related Report
      2013 Final Research Report
  • [Book] Induced Cardiomyocytes: Direct reprogramming for cardiac regeneration2013

    • Author(s)
      Ieda M
    • Publisher
      CRC Press,
    • Related Report
      2013 Annual Research Report
  • [Book] 線維芽細胞から直接心筋細胞を誘導する2013

    • Author(s)
      梅井智彦、家田真樹
    • Publisher
      メディカルレビュー社
    • Related Report
      2013 Annual Research Report
  • [Book] ダイレクトリプログラミングによる心筋誘導2013

    • Author(s)
      貞廣威太郎、家田真樹
    • Publisher
      羊土社
    • Related Report
      2013 Annual Research Report
  • [Book] 線維芽細胞から心筋細胞への直接リプログラミング2013

    • Author(s)
      家田真樹
    • Publisher
      医学出版
    • Related Report
      2013 Annual Research Report
  • [Book] 心臓再生の新展開 “Direct Conversion of Fibroblasts into Cardiomyocyte-like Cells by Defined Factors.”2013

    • Author(s)
      家田真樹
    • Publisher
      日本循環器学会
    • Related Report
      2013 Annual Research Report
  • [Book] Cellular Reprogramming and Fate Conversion "Advances in Stem Cell Research" USA2012

    • Author(s)
      Masaki Ieda
    • Publisher
      Humana Press, Springer
    • Related Report
      2013 Final Research Report
  • [Remarks] 報道 朝日新聞、東京新聞、毎日新聞、日本経済新聞、日経産業新聞、産経新聞、読売新聞、日刊工業新聞、中日新聞、TBS ニュース、時事通信、共同通信、日経バイオテク、北海道新聞、河北新報、信濃毎日新聞、静岡新聞、沖縄タイムズ、化学工業日報、西日本新聞、東奥日報、北国新聞、富山新聞、北日本新聞、大阪日日新聞、山陽新聞、日本海新聞、大分合同新聞、宮崎日日新聞、などに関連記事掲載 『ヒトで心筋直接作製』 2013年7月16日

    • Related Report
      2013 Final Research Report

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Published: 2011-08-05   Modified: 2019-07-29  

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