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Development of novel myocardial regeneration therapy for severe heart failure using cellular cardiomyoplasty and gene transfection

Research Project

Project/Area Number 13470274
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Thoracic surgery
Research InstitutionOSAKA UNIVERSITY

Principal Investigator

SAWA Yoshiki  Osaka university graduate school of medicine, Associate professor, 医学部附属病院, 助教授 (00243220)

Co-Investigator(Kenkyū-buntansha) TAKAHASHI Toshiki  Osaka university graduate school of medicine, Lecturer, 医学系研究科, 講師 (50263257)
FUKUSHIMA Norihide  Osaka university graduate school of medicine, Assistant Professor, 医学系研究科, 助手 (30263247)
MATSUDA Hikaru  Osaka university graduate school of medicine, Professor, 医学系研究科, 教授 (00028614)
TAKANO Hiroshi  Osaka university graduate school of medicine, Assistant Professor, 医学系研究科, 助手 (70346196)
MIYAMOTO Yuji  Osaka university graduate school of medicine, Lecturer, 医学系研究科, 講師 (80229898)
西村 元延  大阪大学, 医学系研究科, 助手 (90291442)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥16,600,000 (Direct Cost: ¥16,600,000)
Fiscal Year 2002: ¥6,000,000 (Direct Cost: ¥6,000,000)
Fiscal Year 2001: ¥10,600,000 (Direct Cost: ¥10,600,000)
KeywordsSevere heart failure / cellular cardiomyoplasty / Gene therapy / Combination therapy / Cellular vector / Circulatory Support / Adhesion molecule / Hepatocyte growth factor / 心筋再生 / 遺伝子導入 / Suicide gene therapy / 心筋梗塞
Research Abstract

[Exploitation of new cellular therapy using cellular cardiomyoplasty and gene transfection]
We used a ligation model of proximal left anterior descending coronary artery (LAD) of Lewis rats. Two weeks after LAD ligation, three different treatments were conducted; 1) neonatal rat cardiomyocytes group (T group), 2) HVJ-liposomes bearing the hHGF gene group (H group), and 3) combined (T-H group). The injection site was the scar area of myocardial infarction. For control, culture medium was injected (C group). Echocardiography demonstrated that cardiac performance was significantly ameliorated in the T-H group four and 8 weeks after injection. Contrast echocardiography also showed a marked increase in myocardial perfusion in the T-H group but not in the other groups. In the T-H group, neovascularization and a marked reduction of fibrosis were observed histologically. In an immunohistochemical study, strong staining for beta1-integrin, alpha- and beta-dystroglycan were found principally in the basement membrane of myocytes in the T-H group 8 weeks after transplantation, although there was weak immunoreactivity in the T group.
[Cellular vector and control release of growth factors]
Human HGF cDNA expression plasmid was permanently transfected into NIH3T3 (NIH/HGF). Then, TK was permanently transfected into NIH/HGF (NIH/HGF/TK). After LAD was ligated in the heart of SCID rat, four different materials were transplanted; 1) NIH/HGF , 2) NIH/HGF/TK, oral administration of GCV, 3) NIH3T3 , 4) culture medium (C group). In vitro study, proliferation of NIH/HGF/TK cells was well suppressed under GCV. In vivo study, significant increase of cardiac performance and angiogenesis were observed in the NIH/HGF and the NIH/HGF/TK group 4 weeks after transplantation. Although tumorous lesions were detected in the NIH/HGF group, their growth was completely controlled in the NIH/HGF/TK group.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (17 results)

All Other

All Publications (17 results)

  • [Publications] Miyagawa S, Sawa Y, Taketani S, et al.: "Myocardial regeneration therapy for heart failure : hepatocyte growth factor enhances the effect of cellular cardiomyoplasty"Circulation. 28 ; 105(21). 2556-2561 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ahmet I, Sawa Y, Yamaguchi T et al.: "Gene transfer of hepatocyte growth factor improves angiogenesis and function of chronic ischemic myocardium in canine heart"Ann Thorac Surg. 75(4). 1283-1287 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Funatsu T, Sawa Y, Ohtake S et al.: "Therapeutic angiogenesis in the ischemic canine heart induced by myocardial injection of naked complementary DNA plasmid encoding hepatocyte growth factor"J Thorac Cardiovasc Surg. 124(6). 1099-1105 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ono M, Sawa Y, Matsumoto K, et al.: "In vivo gene transfection with hepatocyte growth factor via the pulmonary artery induces angiogenesis in the rat lung"Circulation. 106(Suppl 1). I264-I269 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 宮川 繁, 澤 芳樹, 竹谷 哲, 松田暉: "心筋梗塞巣に対する心筋細胞移植に関する検討-新生仔心筋細胞の梗塞巣への生着および心機能向上における長期的検討-"心筋の構造と代謝. Vol.23. 113-118 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Miyagawa S: "Annual Report of Osaka University, Academic Achievement"Osaka University. 1 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 宮川 繁, 澤 芳樹, 竹谷 哲, 松田暉: "組織培養工学 Vol.27No.10"ニュー・サイエンス社. 4 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Miyagawa S, Sawa Y, Taketani S, et at.: "Myocardial regeneration therapy for heart failure: hepatocyte growth factor enhances the effect of cellular cardiomyoplasty."Circulation.. 105(21). 2556-2561 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ahmet I, Sawa Y, Yamaguchi T et al.: "Gene transfer of hepatocyte growth factor improves angiogenesis and function of chronic ischemic myocardium in canine heart."Ann Thorac Surg.. 75(4). 1283-1287 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Funatsu T, Sawa Y, Ohtake S et al.: "Therapeutic angiogenesis in the ischemic canine heart induced by myocardial injection of naked complementary DNA plasmid encoding hepatocyte growth factor."J Thorac Cardiovasc Surg.. 124(6). 1099-1105 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ono M, Sawa Y, Matsumoto K, et al.: "In vivo gene transfection with hepatocyte growth factor via the pulmonary artery induces angiogenesis in the rat lung."Circulation.. 106(12 Suppl 1). 1264-1269 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Miyagawa S.: "Myocardial regeneration therapy for heart failure: hepatocyte growth factor enhances the effect of cellular cardiomyoplasty"Annual Report of Osaka University, Academic Achievement 2001-2002. Vol.3. 62

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Miyagawa S: "Myocardial regeneration therapy for heart failure Hepatocyte growth factor enhances the Effect of Cellular Cardiomyoplasty"Circulation. 105. 2556-2561 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Funatsu Toshihiro: "Therapeutic angiogenesis in the ischemic canine heart induced by myocardial injection of naked complementary DNA plasmid encoding hepatocyte growth factor"J Thorac Cardiovasc Surg. 124・6. 1099-1105 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ahmet Ismyle: "Gene transfection of hepatocyte growth factor attenuates cardiac remodeling in the canine heart : A novel gene therapy for cardiomyopathy"J Thorac Cardiovasc Surg. 124・5. 957-963 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 重症心不全に対する心筋再生治療: "心臓病と再生治療"HUMAN SCIENCE. 19-24 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Shigeru Miyagawa: "Myocardial regeneration therapy for heart failure Hepatocyte growth factor enhances the effect of cellular cardiomyoplasty"Circulation. (in press).

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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