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2007 Fiscal Year Final Research Report Summary

Development of regeneration, purification, and transplantation of cardiomyocytes from mouse and common marmoset ES cells

Research Project

Project/Area Number 17209029
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionKeio University

Principal Investigator

FUKUDA Keiichi  Keio University, School of Medicine, Professor (20199227)

Co-Investigator(Kenkyū-buntansha) MURATA Mitsushige  Keio University, School of Medicine, Instructor (30317135)
YUASA Shinsuke  Keio University, School of Medicine, Instructor (90398628)
HATTORI Fumiyuki  Keio University, School of Medicine, Researcher (50398624)
TANIOKA Yoshikuni  Central Institute for Experimental Animals, Animal Experimentation Center, Researcher(non-tenuerd) (10072406)
SASAKI Erika  Central Institute for Experimental Animals, Animal Experimentation Center, Researcher(non-tenuerd) (70390739)
Project Period (FY) 2005 – 2007
Keywordshuman embryonic stem cell / common marmosset / Regeneratie Medicine / Cardiomyocyte / differentiation / Development / Noggin / Cell Transplantation
Research Abstract

This Study tried to establish a novel method for generation, purification, and transplantation of new cardiomyocytes from human and common marmoset ES cells. We found that Noggin induce differentiation from ES cells to antero-lateral mesodermal cell, and that factor X promote differentiation from antero-lateral mesodermal cells to cardiomyocytes. Moreover, we found that Y-receptor is strongly expressed at the early differentiated cardiomyocytes, and administration of Y ligand promoted cell division in embryonic cardiomyocyte in vivo and early differentiated cardiomyocytes from ES cells. In combination with these factors, we can produce cardiomyocytes from marmoset and human ES cells. We also developed a novel method to purify cardiomyocytes from the mixture of cells by using mitochondria-specific incorporated dye. We transplanted the cardiomyocytes purified by this method, and the grafted cardiomyocytes can eliminate teratoma formation. Moreover, we also developed a novel method to enhance the cell survival after transplantation by a re-aggregation method. The grafted cell survival by needle injection into the heart was less than 1%, while this method can improve the efficiency up to 90%. We transplanted the purified cardiomyocytes into immuno-deficient mouse and common marmoset monkeys, In combination with these various techniques, we developed an efficient method to purify cardiomyocytes.

  • Research Products

    (11 results)

All 2008 2007 2006 2005

All Journal Article (7 results) (of which Peer Reviewed: 3 results) Presentation (2 results) Book (1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Common marmoset embryonic stem cell can differentiate into Cardio myocytes.2008

    • Author(s)
      Chen H, Hattori F, Murata M, Fukuda K, et al.
    • Journal Title

      Biophys Biochem Res Comm. 369

      Pages: 801-806

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Common marmoset embryonic stem cell can differentiate into Cardiomyocytes.2008

    • Author(s)
      Hao Chen, Fumiyuki Hattori, Mitsushige Murata, Weizhen Li, Shinsuke Yuasa, Takeshi Onizuka, Kenichiro Shimoji, Yohei Ohno, Erika Sasaki, Kensuke Kimura, Daihiko Hakuno, Motoaki Sano, Shinji Makino, Satoshi Ogawa, Keiichi Fukuda.
    • Journal Title

      Biophys Biochem Res Comm. 369

      Pages: 801-806

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Chondromodulin-I mainstains cardiac valvular function by preventing angiogenesis.2006

    • Author(s)
      Masatoyo Yoshioka, Keicihi Fukuda, et al.
    • Journal Title

      Nature Medicine 12

      Pages: 1151-1159

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Chondromodulin-I maintains cardiac valvular function by preventing angiogenesis.2006

    • Author(s)
      Masatoyo Yoshioka, Shinsuke Yuasa, Kensuke Kimura, Naritaka Kimura, Keisuke Matsumura, Takayuki Shiomi, Chisa Shukunami, Yasunori Okada, Makio Mukai, Hankei Shin, Ryohei Yozu, Masataka Sata, Satoshi Ogawa, Yuji Hiraki, Keiichi Fukuda.
    • Journal Title

      Nat Med 12

      Pages: 1151-1159

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Mesenchymal stem cell-derived cardiomyogenic cells. Cardiac Regeneration and Stem Cell Therapy.2006

    • Author(s)
      Keiichi Fukuda, Jun Fujita, Daihiko Hakuno, Shinji Makino.
    • Journal Title

      edited by Leri A, Anversa P, Frishman WH. Blackwell Publishing. Oxford, UK.

      Pages: 37-45

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Transient and strong inhibition of BMP signals by Noggin induces cardiomyocyte differentiation in murine embryonic stem cells.2005

    • Author(s)
      Shnsuke Yuasa, Keiichi Fukuda, et al.
    • Journal Title

      Nature Biotechnology 23

      Pages: 607-611

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Transient and strong inhibition of BMP signals by Noggin induces cardiomyocyte differentiation in murine embryonic stem cells.2005

    • Author(s)
      Shinsuke Yuasa, Yuji Itabashi, Uichi Koshimizu, Tomofumi Tanaka, Keijiro Sugimura, Masayoshi Kinoshita, Fumiyuki Hattori, Shin-ichi Fukami, Takuya Shimazaki, Satoshi Ogawa, Hideyuki Okano, Keiichi Fukuda.
    • Journal Title

      Nature Biotechnology 23

      Pages: 607-611

    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Characterization of Common Marmoset Monkey ES Cell-Derived Cardiomyocytes and Formation of Cardiac Cell-Sheet.2008

    • Author(s)
      akeshi Onizuka, Kenichiro Shimoji, Mitsushige Murata, Kensuke Kimura, Shinji Makino, Motoaki Sano, Keiichi Fukuda.
    • Organizer
      The 72^<nd> Annual Scientific Meeting of the Japanese Circulation Society.
    • Place of Presentation
      Fukuoka, Japan
    • Year and Date
      20080328-20080330
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Characterization of Common Marmoset Monkey ES Cell-Derived Cardiomyocytes and Formation of Cardiac Cell-Sheet.2008

    • Author(s)
      Hao C, Hattori F, Onizaka. T, Yuasa S, Shimoji K, Ohno Y, Hara M, Fukuda K.
    • Organizer
      第72回日本循環器学会
    • Place of Presentation
      福岡国際会議場
    • Year and Date
      2008-03-30
    • Description
      「研究成果報告書概要(和文)」より
  • [Book] Mesenchymal stem cell-derived cardiomyogenic cells, “Cardiac Regeneration and Stem Cell Therapy"2006

    • Author(s)
      Keiichi Fukuda. Jun Fujita, et al.
    • Total Pages
      37-45
    • Publisher
      Blackwell Publishing. Oxford, UK, 2006.
    • Description
      「研究成果報告書概要(和文)」より
  • [Patent(Industrial Property Rights)] 心筋細胞の細胞塊作成方法および心筋細胞塊の用途2007

    • Inventor(s)
      服部文幸, 福田恵一
    • Industrial Property Rights Holder
      アスビオフアーマ, 学校法人慶應義塾
    • Industrial Property Number
      特願2007-200246
    • Filing Date
      2007-07-31
    • Description
      「研究成果報告書概要(和文)」より

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Published: 2010-06-09  

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