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A Novel Gene Therapy with Bone Marrow Stem Cell Homing

Research Project

Project/Area Number 18591431
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General surgery
Research InstitutionChiba University

Principal Investigator

MITSUHASHI Noboru  Chiba University, Research Center for Frontier Medical Engineering, Associate Professor (80400985)

Co-Investigator(Kenkyū-buntansha) MIYAZAKI Masaru  Chiba University, Graduate School of Medicine, Professor (70166156)
KIMURA Fumio  Chiba University, Graduate School of Medicine, Associate Professor (70334208)
SHIMIZU Hiroaki  Chiba University, Graduate School of Medicine, Associate Professor (80272318)
YOSHIDOME Hiroyuki  Chiba University, Graduate School of Medicine, Associate Professor (10312935)
OHTSUKA Masayuki  Chiba University, Graduate School of Medicine, Assistant Professor (90334185)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥4,010,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥510,000)
Fiscal Year 2007: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
KeywordsBone Marrow Stem Cell / VEGF / AFP / Homing
Research Abstract

In this study, we attempted to establish a novel gene therapy with bone marrow mesenchymal stem cell. At first, we compared mRNA expression of chemokines, growth factors, and those receptors using quantitative RT-PCR between human hepatocellular carcinoma and adjacent tissues. We found difference of several genes expression. As a target gene for treatment, we selected alpha-fetoprotein (AFP) because AFP has properties of cell proliferation and anti-apoptosis. The expression of AFP in AFP transfected cell was confirmed by immunohistochemistry and enzyme linked immuno-sorbent assay (ELISA). AFP has confirmed as a stimulator of proliferation and an inhibitor of apoptosis of bone marrow MSC. As a target gene for homing, we selected VEGF/VEGFR-1 system because VEGF has known as a potent chemoattractant for bone marrow MSC. We also confirmed the expression of VEGFR-1 in mouse bone marrow MSC in protein level by flow cytometery. VEGF simulated migration of mouse bone marrow MSC in vitro. The double transfection of VEGFR-1 and AFP was performed using retrovirus vector. The double transfected cells showed stable expression of both VEGFR-1 and AFP assessed by flow cytometry and ELISA. Migration of double transfected cells to VEGF was confirmed using migration assay in vitro. Then, we performed subcutaneous injection of VEGF at back of mouse and intra venous injection of double transfected cells. Accumulation of double transfected cells at the back was confirmed by histological examination. Further, we confirmed migrated double transfected cells expressed AFP by histrological examination and ELISA. In conclusion, we established double transfected cells that could home to the lesion and produce the therapeutic molecule. This system may be a useful strategy for various kinds of diseases.

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (18 results)

All 2007 Other

All Journal Article (6 results) (of which Peer Reviewed: 3 results) Presentation (10 results) Remarks (2 results)

  • [Journal Article] Rat chemokine CXCLll: structure, tissue distribution, function and expression incardiac transplantation models.2007

    • Author(s)
      Noboru Mitsuhashi, et. al.
    • Journal Title

      Mol Cell Biochem. 296

      Pages: 1-9

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Rat chemokine CXCL11: structure, tissue distribution, function and expression in cardiac transplantation models2007

    • Author(s)
      Noboru Mitsuhashi, et. al.
    • Journal Title

      Mol Cell Biochem 296

      Pages: 1-9

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Clinical significance of α-Fetoprotein; involvement on proliferation, angiogenesis, and apoptosis of hepatocellular carcinoma

    • Author(s)
      Noboru Mitsuhashi, et. al.
    • Journal Title

      J Gastroenterol Hepatol. (In press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Angiopoietin-2 levels in the hepatic vein as a useful predictor of tumor invasiveness and prognosis in human hepatocellular carcinoma.

    • Author(s)
      Kuboki S, et. al.
    • Journal Title

      J Gastroenterol Hepatol. (In press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Clinical significance of α-Fetoprotein; involvement on proliferation, angiogenesis, and apoptosis of hepatocellular carcinoma

    • Author(s)
      Noboru Mitsuhashi, et. al.
    • Journal Title

      J Gastroenterol Hepatol (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Angiopoietin-2 levels in the hepatic vein as a useful predictor of tumor invasiveness and prognosis in human hepatocellular carcinoma

    • Author(s)
      Satoshi Kuboki, et. al.
    • Journal Title

      J Gastroenterol Hepatol (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Small Interfering RNA Administration against AFP Inhibits Proliferation and Anti-apoptotic Properties of Hepatocellular Carcinoma Cell Lines.2007

    • Author(s)
      Noboru Mitsuhashi, et. al.
    • Organizer
      European Cancer Conference 14th (ECCO14)
    • Place of Presentation
      Barcelona, Spain
    • Year and Date
      2007-09-24
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Small Interfering RNA Administration against AFP Inhibits Proliferation and Anti-apoptotic Properties of Hepatocellular Carcinoma Cell Lines2007

    • Author(s)
      Noboru Mitsuhashi, et. al.
    • Organizer
      European Cancer Conference 14th
    • Place of Presentation
      Barcelona, Spain
    • Year and Date
      2007-09-24
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Small Interfering RNA Administration against AFP Inhibits Proliferation and Anti-apoptotic Properties of Hepatocellular Carcinoma Cell Lines.2007

    • Author(s)
      Noboru Mitsuhashi, et. al.
    • Organizer
      European Cancer Conference 14th(ECCO14)
    • Place of Presentation
      Barcelona,Spain
    • Year and Date
      2007-09-24
    • Related Report
      2007 Annual Research Report
  • [Presentation] 肝細胞癌におけるAFPの役割2007

    • Author(s)
      三橋 登 他
    • Organizer
      第62回日本消化器外科学会総会
    • Place of Presentation
      東京
    • Year and Date
      2007-07-18
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] Alpha-fetoprotein in Hepatocelular Carcinoma2007

    • Author(s)
      Noboru Mitsuhashi, et. al.
    • Organizer
      Annual Congress of Japanese Society of Gastroenterological Surgery 62nd
    • Place of Presentation
      Tokyo, Japan
    • Year and Date
      2007-07-18
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 肝細胞癌におけるAFP発現の意義と発現制御の基礎的検討2007

    • Author(s)
      三橋 登 他
    • Organizer
      第43回日本肝癌研究会
    • Place of Presentation
      東京
    • Year and Date
      2007-06-21
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] Significance of AFP expression in Hepatocellular Carcinoma2007

    • Author(s)
      Noboru Mitsuhashi, et. al.
    • Organizer
      Annual Congress of Liver Cancer Study Group ofJapan 43rd
    • Place of Presentation
      Tokyo, Japan
    • Year and Date
      2007-06-21
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] VEGF, PIGF/VEGFR-1システムは間葉系幹細胞の同種移植心へのホーミングと増殖に関与する2007

    • Author(s)
      三橋 登 他
    • Organizer
      第107回日本外科学会総会
    • Place of Presentation
      大阪
    • Year and Date
      2007-04-12
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Involvement of VEGF, P1GF/VEGFR-1 system in Mesenchymal Stem Cell homing to allogeneic heart graft2007

    • Author(s)
      Noboru Mitsuhashi, et. al.
    • Organizer
      Annual Congress of Japan Surgical Society 108th
    • Place of Presentation
      Osaka, Japan
    • Year and Date
      2007-04-12
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] VEGF,PIGF/VEGFR-1システムは間葉系幹細胞の同種移植心へのホーミングと増殖に関与する2007

    • Author(s)
      三橋 登, 他
    • Organizer
      第107回日本外科学会総会
    • Place of Presentation
      大阪
    • Year and Date
      2007-04-12
    • Related Report
      2007 Annual Research Report
  • [Remarks] 「研究成果報告書概要(和文)」より

    • URL

      http://www.cfme.chiba-u.jp/bumon/seitainano/bumon4.htm

    • Related Report
      2007 Final Research Report Summary
  • [Remarks]

    • URL

      http://www.cfme.chiba-u.jp/bumon/seitainano/bumon4.htm

    • Related Report
      2007 Annual Research Report

URL: 

Published: 2006-04-01   Modified: 2016-04-21  

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