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Fetal Cardiac Cell Transplantation and Transcription Factor of the Heart

Research Project

Project/Area Number 07457299
Research Category

Grant-in-Aid for Scientific Research (B)

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

Principal Investigator

KITAMURA Soichiro  Nara Medical Univ., Dept.Surgery III,Professor, 医学部, 教授 (10028607)

Co-Investigator(Kenkyū-buntansha) UENO Satoshi  Nara Medical Univ., Dept.Genetics, Associated Professor, 医学部, 助教授 (40184949)
NIWAYA Kazuo  Nara Medical Univ., Dept.Surgery III,Assistant, 医学部, 助手 (30254501)
KOBAYASHI Syuichi  Nara Medical Univ., Dept.Surgery III,Assistant, 医学部, 助手 (50201489)
Project Period (FY) 1995 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥5,800,000 (Direct Cost: ¥5,800,000)
Fiscal Year 1996: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1995: ¥3,300,000 (Direct Cost: ¥3,300,000)
KeywordsGENE TRANSFER / CELL TRANSPLANTATION / RETROVIRUS / ADENOVIRUS / TRANSCRIPTION FACTOR / FETAL CELLS / CELL CYCLE / 心筋細胞移植
Research Abstract

Cardiac cell transplantation is the one potential treatment for acute or chronic heart failure with a significant loss of myocardium. Prerequisites for cellular transplantation to the heart to be successful include the followings : 1. formation of a new functional syncytium between grafted and host cardiomyocytes, 2. the number of grafted cells large enough to improve cardiac function, and 3. long-term graft survival. The transfer of a therapeutic gene into the cells to be grafted may possibly solve these obstacles. To begin with, we performed cell transplantation of the gene transferred fetal myocardial cells with recombinant plasmids, retroviruses, or adenoviruses coding beta-galactosidase. We found that adenovirus vector transduced the reporter gene into cultured cardiomyocytes without any damage, and that the grafted cardiac cells survived and expressed beta-gal for 12 weeks. The gap junctions were formed between the host cardiomyocytes and grafted cells. On the other hand, the plasmid vectors was little efficient for gene transfer, and the gene transferred grafted cells by the retroviruses could not form the gap junction in the host hearts. Candidates for gene transfer are the genes to make cardiomyocytes proliferate or to make embryonic cells differentiate into cardiomyocytes. However, the mechanisms of regulating the proliferation and differentiation of cardiomyocytes are unclear. We examined the expression patterns of cell cycle relating genes (Cyclin D1-3, Cyclin dependent kinase inhibitors (p15, p16, p21, p27, p57)) on P19 EC cells differentiating into cardiomyocytes under alpha MEM culture medium containing 1% DMSO.The results suggested that Cyclin D2 and p21 might play a role in induction of differentiation into cardiomyocytes. The function of p27 and p57 may be a strong inhibition of proliferation in process of differentiation into cardiomyocytes.

Report

(3 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report
  • Research Products

    (14 results)

All Other

All Publications (14 results)

  • [Publications] Satoshi Gojo et al: "Transplantation of Genetically Marked Cardiac Muscle Cells" The Journal of Thoracic and Cardiovascular Surgery. 113(1). 10-16 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Satoshi Gojo et al: "Ex Vivo Gene Transfer into Myocardium using Replication-Defective Retrovirus" Cell Transplantation. 5. S81-S84 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Satoshi Gojo et al: "Ex Vivo Gene Transfer to Transplanted Heart Grafts using Adenoviral Vecto" Transplantation Proceeding. 28. 1818-1819 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 北村 惣一郎: "心臓血管外科領域における遺伝子導入の研究" 循環器専門医. 4(1). 155-161 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Satoshi Gojo, Soichiro Kitamura, Wilfred T.V.Germeraad, Yoshitsugu Yoshida, Kazuo Niwaya, Kanji Kawachi: "Ex vivo gene transfer into myocardium using replication-defective retrovirus." Cell Transplantation. Vol.5 (5S-1). S81-84 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Satoshi Gojo, Soichiro Kitamura, Kazuo Niwaya Yoshitsugu Yoshida, Hidehito Sakaguchi, Kanji Kawachi: "Ex vivo gene transfer to transplanted heart grafts usning adenoviral vector." Transplantation Proc.Vol.28 (3). 1818-1819 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Satoshi Gojo, Soiciro Kitamura, Osamu Hatano, Akira Takakusu, Kenji Hashimoto, Yumi Kanegae, Izumu Saito: "Transplantation of genetically marked cardiac muscle cells." J.Thorac.Cardiovasc.Surg.113 (1). 10-18 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Satoshi Gojo et al: "Transplantation of Genetically Marked Cardiac Muscle Cells" The Journal of Thoracic and Caediovascular Surgery. 113 (1). 10-16 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Satoshi Gojo et al: "Ex Vivo Gene Transfer into Myocardium using Replication-Defective Retrovirus" Cell Transplantation. 5. S81-S84 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Satoshi Gojo et al: "Ex Vivo Gene Transfer to Transplanted Heart Grafts using Adenoviral Vecto" Transplantation Proceeding. 28. 1818-1819 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 北村惣一郎: "心臓血管外科領域における遺伝子導入の研究" 循環器専門医. 4 (1). 155-161 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 北村惣一郎: "心臓血管外科領域における遺伝子導入の研究" 循環器専門医. 4巻. 155-161 (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Satoshi Gojo: "Ex vivo gene transfer into myocardium using replication-defective retrovirus." Cell Transplantation.(in press). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Satoshi Gojo: "Ex vivo gene transfer to transplanted heart grafts using adenoviral vector." Transplantation Proceeding.(in press). (1996)

    • Related Report
      1995 Annual Research Report

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Published: 1995-04-01   Modified: 2016-04-21  

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