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Efficient and safe reprogramming of fibroblasts into cardiomyocytes with Sendai viral vectors

Research Project

Project/Area Number 25670394
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Cardiovascular medicine
Research InstitutionKeio University

Principal Investigator

Ieda Masaki  慶應義塾大学, 医学部, 講師 (70296557)

Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords心臓 / 再生 / 心筋 / リプログラミング / センダイウイルス
Outline of Final Research Achievements

Heart disease remains a leading cause of death worldwide, and new therapies are highly demanded. As cardiomyocytes are terminally differentiated cells, regenerative therapy has emerged as an attractive approach for the treatment of heart failure. Direct cardiac reprogramming approach might be a powerful strategy toward this treatment. We reported that a combination of three cardiac-specific transcription factors, Gata4, Mef2c, and Tbx5 (GMT), could directly reprogram fibroblasts into cardiomyocyte-like cells in vitro and in vivo. The aim of this study is to develop new Sendai viral vectors (SeVs) which overexpress reprogramming factors without genomic integration, and to determine the efficiency and safety of cardiac reprograming with SeVs. We generated SeVs vectors containing GMT and found that the vector could efficiently reprogram mouse fibroblasts inot cardiomyocyte-like cells in vitro.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (47 results)

All 2016 2015 2014 2013

All Journal Article (14 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 14 results,  Open Access: 2 results,  Acknowledgement Compliant: 7 results) Presentation (15 results) (of which Int'l Joint Research: 2 results,  Invited: 15 results) Book (15 results) Patent(Industrial Property Rights) (3 results) (of which Overseas: 1 results)

  • [Journal Article] Effective Cibenzoline Treatment in a Patient With Midventricular Obstruction After Transcatheter Aortic Valve Implantation.2016

    • Author(s)
      Isobe S, Ieda M, Kohno T, Nishiyama T, Maekawa Y, Tsuruta H, Murata M, Yashima F, Yanagisawa R, Tanaka M, Inami S, Nasuno T, Haruyama A, Sano M, Hayashida K, Fukuda K.
    • Journal Title

      Circ Heart Fail

      Volume: 9 Issue: 1

    • DOI

      10.1161/circheartfailure.115.002629

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Neural crest-derived resident cardiac cells contribute to the restoration of adrenergic function of transplanted heart in rodent.2016

    • Author(s)
      Tamura Y, Sano M, Nakamura H, Ito K, Sato Y, Shinmura K, Ieda M, Fujita J, Kurosawa H, Ogawa S, Nakano S, Matsuzaki M, Fukuda K.
    • Journal Title

      Cardiovasc Res.

      Volume: 109 Issue: 3 Pages: 350-357

    • DOI

      10.1093/cvr/cvv267

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Strategies for heart regeneration: approaches ranging from induced pluripotent stem cells to direct cardiac reprogramming.2015

    • Author(s)
      Yamakawa H, Ieda M.
    • Journal Title

      Int Heart J

      Volume: 56 Issue: 6 Pages: 1-5

    • DOI

      10.1016/j.stemcr.2015.10.019

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Direct Cardiac Reprogramming: Progress and Challenges in Basic Biology and Clinical Applications.2015

    • Author(s)
      Sadahiro T, Yamanaka S, Ieda M.
    • Journal Title

      Circ Res.

      Volume: 116 Issue: 8 Pages: 1378-1391

    • DOI

      10.1161/circresaha.116.305374

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Stoichiometry of transcription factors is critical for cardiac reprogramming.2015

    • Author(s)
      Muraoka N, Ieda M
    • Journal Title

      Circ Res

      Volume: 116 Issue: 2 Pages: 216-218

    • DOI

      10.1161/circresaha.114.305696

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Strategies for Heart Regeneration2015

    • Author(s)
      Yamakawa H, Ieda M
    • Journal Title

      International Heart Journal

      Volume: 56 Issue: 1 Pages: 1-5

    • DOI

      10.1536/ihj.14-344

    • NAID

      130004941301

    • ISSN
      1349-2365, 1349-3299
    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] MiR-133 promotes cardiac reprogramming by directly repressing Snai1 and silencing fibroblast signatures.2014

    • Author(s)
      Mizuha Akiyama, Rie Wada, Kohei Inagawa, Takahiko Nishiyama, Ruri Kaneda, Toru Fukuda, Shu Takeda, Shugo Tohyama, Hisayuki Hashimoto, Yoshifumi Kawamura, Naoki Goshima, Ryo Aeba, Hiroyuki Yamagishi, Keiichi Fukuda, Masaki Ieda
    • Journal Title

      EMBO J.

      Volume: 33 Issue: 14 Pages: 1565-1581

    • DOI

      10.15252/embj.201387605

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Multidisciplinary approach to the treatment of cardiac AA amyloidosis and aortic stenosis due to Castleman's disease: a hybrid therapy with tocilizumab and aortic valve replacement.2014

    • Author(s)
      Shirakawa K, Egashira T, Ieda M, Kawaguchi S, Okamoto K, Kudo M, Yokoyama K, Tsuruta H, Murata M, Mikami S, Anzai A, Hayashida K, Kohno T, Maekawa Y, Sano M, Yozu R, Fukuda K.
    • Journal Title

      Int J Cardiol.

      Volume: 173 Issue: 2 Pages: e9-e11

    • DOI

      10.1016/j.ijcard.2014.03.054

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Direct Reprogramming into Cardiomyocytes.2014

    • Author(s)
      Miyamoto K, Ieda M
    • Journal Title

      Inflammation and Regeneration

      Volume: 34 Pages: 217-223

    • NAID

      130004943868

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Direct Reprogramming of Fibroblasts into Myocytes to Reverse Fibrosis2014

    • Author(s)
      Muraoka N, Ieda M
    • Journal Title

      Annu Rev Physiol

      Volume: 76 Issue: 1 Pages: 21-37

    • DOI

      10.1146/annurev-physiol-021113-170301

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

    • Author(s)
      Ieda M.
    • Journal Title

      Keio J Med.

      Volume: 62 Pages: 99-106

    • Related Report
      2013 Research-status 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 Research-status Report
    • Peer Reviewed
  • [Presentation] ダイレクトリプログラミングによる心筋再生2016

    • Author(s)
      家田真樹
    • Organizer
      第15回日本再生医療学会シンポジウム
    • Place of Presentation
      大阪国際会議場(大阪府・大阪市)
    • Year and Date
      2016-03-17
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 心筋直接リプログラミング制御因子の同定と応用2015

    • Author(s)
      家田真樹
    • Organizer
      第38回日本分子生物学会
    • Place of Presentation
      神戸ポートアイランド(兵庫県・神戸市)
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Direct Cardiac Reprogramming for Heart Repair2015

    • Author(s)
      Masaki Ieda
    • Organizer
      9th International Cell Therapy Conference
    • Place of Presentation
      Seoul, South Korea
    • Year and Date
      2015-10-23
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Reprogramming of Cardiac fibroblasts2015

    • Author(s)
      Masaki Ieda
    • Organizer
      American Heart Association Basic Cardiovascular Sciences 2015
    • Place of Presentation
      New Orleans, LA, USA.
    • Year and Date
      2015-07-13
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 心筋直接リプログラミングによる心不全治療2015

    • Author(s)
      家田真樹
    • Organizer
      第79回日本循環器学会学術集会
    • Place of Presentation
      大阪国際会議場(大阪府・大阪市)
    • Year and Date
      2015-04-24
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Reprogramming Fibroblasts into Cardiomyocytes for Heart Repair2014

    • Author(s)
      Masaki Ieda
    • Organizer
      CURRENT TRENDS IN BIOMEDICINE 2014
    • Place of Presentation
      Baeza, Spain
    • Year and Date
      2014-10-06 – 2014-10-08
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] 心筋直接誘導による心臓再生2014

    • Author(s)
      家田真樹
    • Organizer
      再生医療公開フォーラム
    • Place of Presentation
      東京
    • Year and Date
      2014-09-28
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] Discovery, Progress, and Challenges of Direct Cardiac Reprogramming for Heart Repair2014

    • Author(s)
      Masaki Ieda
    • Organizer
      American Heart Association Basic Cardiovascular Sciences 2014
    • Place of Presentation
      Las Vegas, Nevada, USA
    • Year and Date
      2014-07-14 – 2014-07-17
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] Generation of Cardiomyocytes from fibroblasts by direct reprogramming technology2014

    • Author(s)
      Masaki Ieda
    • Organizer
      THE UEHARA MEMORIAL FOUNDATION SYMPOSIUM 2014,
    • Place of Presentation
      Tokyo, Japan
    • Year and Date
      2014-06-15 – 2014-06-17
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] 心筋直接誘導による新しい心臓再生法の開発2014

    • Author(s)
      家田真樹
    • Organizer
      第87回日本組織培養学会シンポジウム
    • Place of Presentation
      東京
    • Year and Date
      2014-05-29 – 2014-05-30
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] Bypassing Pluripotency2014

    • Author(s)
      Masaki Ieda
    • Organizer
      19th Medical Research Conference
    • Place of Presentation
      Hong Kong, China
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] Direct Cardiac Reprogramming by Defined Factors2013

    • Author(s)
      Masaki Ieda
    • Organizer
      International Society for Heart Research
    • Place of Presentation
      San Diego, USA
    • Related Report
      2013 Research-status 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 Research-status 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 Research-status 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 Research-status Report
    • Invited
  • [Book] A diversity of emerging physiological and pathological activities2015

    • Author(s)
      Masaki Ieda
    • Publisher
      Springer
    • Related Report
      2015 Annual Research Report
  • [Book] 心筋直接リプログラミングによる新しい心臓再生法の開発2015

    • Author(s)
      家田真樹
    • Publisher
      最新医学
    • Related Report
      2015 Annual Research Report
  • [Book] ダイレクトリプログラミング 線維芽細胞から心筋細胞2015

    • Author(s)
      家田真樹
    • Publisher
      秀潤社
    • Related Report
      2015 Annual Research Report
  • [Book] iCM細胞の樹立と臨床応用への展望2015

    • Author(s)
      家田真樹
    • Publisher
      Heart View
    • Related Report
      2015 Annual Research Report
  • [Book] iPS細胞と心筋直接リプログラミングによる心臓再生医療2015

    • Author(s)
      村岡直人、家田真樹
    • Publisher
      Heart View
    • Related Report
      2015 Annual Research Report
  • [Book] 心筋の直接誘導2015

    • Author(s)
      礒見まり、家田真樹
    • Publisher
      羊土社
    • Related Report
      2014 Research-status Report
  • [Book] 直接リプログラミング研究の進展とその応用2014

    • Author(s)
      家田真樹
    • Publisher
      細胞
    • Related Report
      2014 Research-status Report
  • [Book] 心臓線維芽細胞と心筋細胞2014

    • Author(s)
      家田真樹
    • Publisher
      秀潤社
    • Related Report
      2014 Research-status Report
  • [Book] ips細胞と心筋ダイレクトリプログラミングによる心血管老化治療の展望2014

    • Author(s)
      家田真樹
    • Publisher
      科学評論社
    • Related Report
      2014 Research-status Report
  • [Book] microRNA-133はSnai1抑制および線維芽細胞特性消去により心筋直接誘導を促進する2014

    • Author(s)
      村岡直人、家田真樹
    • Publisher
      メディカルレビュー
    • Related Report
      2014 Research-status Report
  • [Book] Induced Cardiomyocytes: Direct reprogramming for cardiac regeneration2013

    • Author(s)
      Ieda M
    • Publisher
      CRC Press
    • Related Report
      2013 Research-status 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 Research-status 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 Research-status 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 Research-status 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 Research-status Report
  • [Patent(Industrial Property Rights)] 心筋様細胞の作製方法及びそれに用いる心筋様細胞の作製用組成物2015

    • Inventor(s)
      井上 誠、弘中 孝史、宮本和享、家田真樹
    • Industrial Property Rights Holder
      井上 誠、弘中 孝史、宮本和享、家田真樹
    • Industrial Property Rights Type
      特許
    • Filing Date
      2015-09-30
    • Related Report
      2015 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 心筋様細胞の作製方法及びそれに用いる培地2014

    • Inventor(s)
      山川裕之、家田真樹
    • Industrial Property Rights Holder
      山川裕之、家田真樹
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2014-096729
    • Filing Date
      2014-05-08
    • Related Report
      2014 Research-status Report
  • [Patent(Industrial Property Rights)] 心筋様細胞の作製方法及びそれに用いる心筋様細胞の作製用組成物2014

    • Inventor(s)
      井上 誠、弘中 孝史、宮本和享、家田真樹
    • Industrial Property Rights Holder
      井上 誠、弘中 孝史、宮本和享、家田真樹
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2014-205988
    • Filing Date
      2014-10-06
    • Related Report
      2014 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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