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Morphological, Electrophysiological and Molecular Analysis of the Cardiomyocytes Defferentiated From Bone Marrow Mesenchymal Stem Cells

Research Project

Project/Area Number 10470170
Research Category

Grant-in-Aid for Scientific Research (B)

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

Principal Investigator

OGAWA Satoshi  KEIO UNIVERSITY, DEPT. OF MEDICINE, PROFESSOR, 医学部, 教授 (90124940)

Co-Investigator(Kenkyū-buntansha) SANO Motoaki  KEIO UNIVERSITY, DEPT. OF MEDICINE, INSTRUCTOR, 医学部, 助手 (30265798)
KODAMA Hiroaki  KEIO UNIVERSITY, DEPT. OF MEDICINE, INSTRUCTOR, 医学部, 助手 (70225457)
FUKUDA Keiichi  KEIO UNIVERSITY, DEPT. OF MEDICINE, ASSISTANT PROFESSOR, 医学部, 講師 (20199227)
KATO Takahiro  KEIO UNIVERSITY, DEPT. OF MEDICINE, INSTRUCTOR, 医学部, 助手 (60276219)
TAKAHASHI Toshiyuki  KEIO UNIVERSITY, DEPT. OF MEDICINE, INSTRUCTOR, 医学部, 助手 (20265804)
Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥13,000,000 (Direct Cost: ¥13,000,000)
Fiscal Year 1999: ¥4,800,000 (Direct Cost: ¥4,800,000)
Fiscal Year 1998: ¥8,200,000 (Direct Cost: ¥8,200,000)
KeywordsBone marrow stromal cell / Cardiomyocyte / Stem cell / Regenerative medicine / Differentiation / cardiomyocyte / differentiation / mnarrow stroma / development
Research Abstract

We have isolated a cardiomyogenic cell line from murine bone marrow stromal cells. The cells showed a fibroblast-like morphology, but the morphology changed after 5-azacytidine treatment in approximately 30% of the cells; they connected with adjoining cells after 1 week, formed myotube-like structures and began spontaneous beating after 2 weeks, and beat synchronously after 3 weeks. The expressed ANP and BNP. Electron microscopy revealed a cardiomyocyte-like ultrastructure including typical sarcomeres and atrial granules. These cells had several types of action potentials; sinus node-like and ventricular cell-like action potentials. All cells had a long action potential duration or plateau, a relatively shallow resting membrane potential, and a pacemaker-like late diastolic slow depolarization. Analysis of the isoform of contractile protein genes, such as myosin heavy chain, myosin light chain and α-actin, indicated that their muscle Nkx2.5/Csx, GATA4, TEF-1 and MEF-2C mRNA before 5-azacytidine treatment, and expressed MEF-2A and MEF-2D after treatment. The use of adult tissues as a source of cardiomyocytes makes this system particularly appropriate for the development of gene therapy strategies for heart disease. This new cell line provides a powerful model for the study of cardiomyocytes differentiation.

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • Research Products

    (25 results)

All Other

All Publications (25 results)

  • [Publications] Tomohiro Manabe, Satoshi Ogawa: "Hypertrophic stimuli augment expression of cMG1/ERF-1, a putative zinc-finger motif transcription factor, in rat cardiomyosytes"FEBS Letters. 463. 39-42 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hiroaki Kodama, Satoshi Ogawa: "Significance of Raf-1/MEK/REK cascade compared with JAK/STAT and PI3-K pathway in gp 130-mediates cardiac Hypertrophy"American Journal of Physiology. (in press). (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Motoaki Sano, Satoshi Ogawa: "Autocrime/Paracrine Secretion of IL-6 Family Cytokines causes Angiotensin II-induced Delayed STAT3 Activation"Biochem. Biphys. Res. Com.. (in press). (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tosiyuki Takahashi, Satoshi Ogawa: "Characterization of IGF-1-induced activation of the JAK/STAT pathway in rat cardiomyocytes"Circulation Research. 85. 884-891 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hideaki Kanki, Satoshi Ogawa: "Comparison of nerve growth factor mRNA expression in cardiac and skeletal muscle in streptozotacin-induced diabetic mice"Life Science. 22. 2305-2312 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Motoaki Sano, Satoshi Ogawa: "IL-6 Family of Cytokines mediate angiotensin II-induced cardiac hypertrophy in rodent cardiomyocytes"Circulation Research. 86(in press). (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Shinji Makino, Keiich Fukuda, et al: "Cardimyocytes can be generated from marrow stromal cells in vitro"J. Clin. Invest.. 103. 697-705 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Keiich Fukuda, Satoshi Ogawa: "Establishment of Cardiomyo genic cell Line from Marrow Strama"Elsevier(in press). (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tomohiro Manaba, Satoshi Ogawa et al.: "Hypertrophic stimuli augment expression of cMG1/ERF-1, a putative zinc-finger motif transcription factor, in rat cardiomyocytes"FEBS Letters. 463. 39-42 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hiroaki Kodama, Satoshi Ogawa et al.: "Significance of Raf-1/MEK/ERK cascade compared with JAK/STAT and PI3-K pathway in gp130-mediated Cardiac Hypertrophy"American Journal of Physiology. (in press). (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Motoaki Sano, Satoshi Ogawa et al.: "Autocrine/Paracrine Secretion of IL-6 Family Cytokines Causes Angiotensin II-induced Delayed STAT3 Activation"Biochem. Biphys. Res. Com.. (in press). (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Toshiyuki Takahashi, satoshi Ogawa et al.: "Characterization of IGF-1-induced activation of the JAK/STAT pathway in rat cardiomyocytes"Circulation Research. 85. 884-891 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hideaki Kanki, Satoshi Ogawa et al.: "Comparison of nerve growth factor mRNA expression in cardiac and skeletal muscle in streptozotocin-induced diabetic mice"Life Science. 22. 2305-2312 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Motoaki Sano, Satoshi Ogawa et al.: "IL-6 Family of Cytokines mediate angiotensin II-induced cardiac hypertrophy in rodent cardiomyocytes"Circulation Research. 86: (in press). (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Keiichi Fukuda, Satoshi Ogawa: "Establishment of Cardiomyogenic cell Line from Marrow Stroma"Elsevier. (in press). (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tomohiro Manabe,Satoshi Ogawa: "Hypertrophic stimuli augment expression of cMG1/ERF-1,a putative zinc-finger motif transcription factor,in rat cardiomyocytes"FEBS Letters. 463. 39-42 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hiroaki Kodama,Satoshi Ogawa: "Significance of Raf-1/MEK/ERK cascade compared with JAK/STAT and PI3-K pathway in gp130-mediated Cardiar Hypertrophy"American Journal of Physiology. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hiroaki Sano,Satoshi Ogawa: "Autocrine/Paracrine Secretion of IL-6 Family Cytokines Causes Angiotensin IL-Induced Delayed STAT3 Activation"Biochem.Biphys.Res.Com.. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Toshiyuki Takahashi,Satoshi Ogawa: "Characteriaztion of IGF-1-induced activation of the JAK/STAT pathway in rat cardiomyocytes"Circulation Research. 85. 884-891 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hideaki Kanki,Satoshi Ogawa: "Comparison of nerve growth factor mRNA expression in cardiac and skeletal muscle in strep tozotocin-induced diabetic mice"Life Science. 22. 2305-2312 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Motoaki Sano,Satoshi Ogawa: "IL-6 Family of Cytokines mediate angiotensin II-induced cardiac hypertrophy in rodent cardiomyocytes"Circulation Research. 86. in press (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Keiich Fukuda,Satoshi Ogawa: "Estabilishment of Cardiomyogenic Cell Line from Marrow Stroma"Elsevier(in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Makino S, Ogawa S,: "Cardiomyocytes can be generated from marrow stromal cells in vitro" The Journal of Clinical Investigation. 103. 697-705 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Pan J, Ogawa S,: "Mechanical stretch activates the JAK/STAT pathway in rat cardiomyoc" Circulation Research. (in press). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Murata M, Ogawa S: "Leukemia inhibitory factor, a potent cardiac hypertrophic cytokine, enhances L-type Ca2+ current and [Ca2+]i transient in rhodent cardiomyocytes." Journal of Molecular and Cellular Cardiology. 31. 237-245 (1999)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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