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骨髄細胞から肝細胞への分化を制御する遺伝子群の同定プロジェクト

Research Project

Project/Area Number 15790348
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Gastroenterology
Research InstitutionYamaguchi University

Principal Investigator

寺井 崇二  山口大学, 医学部, 助手 (00332809)

Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2003: ¥1,800,000 (Direct Cost: ¥1,800,000)
Keywords骨髄細胞 / DNA-Chip / SOM / 可塑性 / 再生医療 / 肝幹細胞 / 分化 転換 / ニッチ / 細胞療法 / DNA-chip
Research Abstract

我々は、自己骨髄細胞を用いた肝臓再生療法の臨床応用を進める基盤モデルとして骨髄細胞から肝細胞への分化評価モデル(GFP/CC14モデル)の開発し、骨髄細胞が持続的肝障害の肝硬変時に肝臓に遊走され肝細胞へ分化・増殖することを明らかにした(JB2003、特公2003-70377)。さらにこのモデルの解析を通じ、骨髄細胞移植により生存率の回復、また肝線維化の改善を発見した(Hepatology 2004,この発見はWiley社よりHepatology News Alert記事とし世界に発信された)。さらに骨髄細胞を用いた再生療法をより効率的に行うための骨髄細胞の肝細胞への分子制御機構を骨髄細胞の肝細胞への分化評価モデルGFP/CC14モデルの解析を通じて、骨髄由来細胞の肝細胞への分化過程に関与する遺伝子群を,DNA-ChipとMicroarray-Self Organization Map(SOM)解析を用い骨髄細胞の投与により誘導された遺伝子群の抽出を目指した。その結果、骨髄細胞の肝細胞への分化は初期には形態形成に関与するHOX,HLH型転写制御分子が関与し、後期においては肝細胞の代謝に関与する分子が誘導されていることが明らかになった(FEBS letters2004)。この結果は骨髄細胞の肝細胞への分化において、発生と同じ遺伝子群が関与することが明らかになった。生データはhttp://liver-roject.med.yamaguchi-u.ac.jp/researchのサイトでホームページにて公開している。)。

Report

(2 results)
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • Research Products

    (14 results)

All 2005 2004 Other

All Journal Article (6 results) Patent(Industrial Property Rights) (1 results) Publications (7 results)

  • [Journal Article] Lesson from the GFP/CCl4 model-Translational Research Project : The development of the cell therapy using autolougous bone marrow cells in liver cirrhosis patients.2005

    • Author(s)
      Terai S
    • Journal Title

      J Hepatobiliary Pancreat Surg. (in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Human Homologue of Maid is a useful marker protein in hepatocarcinogenesis.2005

    • Author(s)
      Takami T
    • Journal Title

      Gastroenterology (in Press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] 骨髄幹細胞移植による肝疾患の治療2005

    • Author(s)
      沖田 極
    • Journal Title

      日本内科学会誌 (In press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Transplantation of bone marrow cells reduces CC14-induced liver fibrosis in mice.2004

    • Author(s)
      Sakaida I
    • Journal Title

      Hepatology 40(6)

      Pages: 1304-1311

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Molecular signature associated with plasticity of bone marrow cell under persistent liver damage by self-organizing-map-based gene expression.2004

    • Author(s)
      Omori K
    • Journal Title

      FEBS Lett. 578(1-2)

      Pages: 10-20

    • Related Report
      2004 Annual Research Report
  • [Journal Article] A subpopulation of bone marrow cells depleted by a novel antibody, anti-Liv8, is useful for cell therapy to repair damaged liver.2004

    • Author(s)
      Yamamoto N
    • Journal Title

      Biochem Biophys Res Commun. 313(4)

      Pages: 1110-1118

    • Related Report
      2004 Annual Research Report
  • [Patent(Industrial Property Rights)] 新規肝細胞癌の腫瘍マーカー抗HHMIgGの発見2004

    • Inventor(s)
      寺井 崇二
    • Industrial Property Rights Holder
      山口TLO
    • Filing Date
      2004-09-14
    • Related Report
      2004 Annual Research Report
  • [Publications] Yokoyama Y: "Proteomic profiling of proteins decreased in hepatocellular carcinoma from patients infected with hepatitis C virus"Proteomics. In press.

    • Related Report
      2003 Annual Research Report
  • [Publications] Sakaida I: "Herbal medicine Sho-saiko-to (TJ-9) increases expression matrix metalloproteinases (MMPs) with reduced expression of tissue inhibitor of metalloproteinases (TIMPs) in rat stellate cell."Life Science. 19;74(18). 2251-2263 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yamamoto N: "A subpopulation of bone marrow cells depleted by a novel antibody, anti-Liv8, is useful for cell therapy to repair damaged liver."Biochem Biophys Res Commun.. 23;313(4). 1110-1118 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Terai S: "An in vivo model for monitoring trans-differentiation of bone marrow cells into functional hepatocytes."J Biochem. 134(4). 551-558 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Sakaida I: "Leptin receptor-deficient Zucker (fa/fa) rat retards the development of pig serum-induced liver fibrosis with Kupffer cell dysfunction."Life Sci.. 73(19). 2491-2501 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Horie T: "L-cysteine administration prevents liver fibrosis by suppressing hepatic stellate cell proliferation and activation."Biochem Biophys Res Commun.. 305(1). 94-100 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Terai S: "Strategy for the development of cell therapy using bone marrow cells to repair damaged liver. Growth/Differentiation and hepatocyte/HCC"Frontier in Hepatology (Stem cell and liver regeneration). 51-56 (2004)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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