Induction of mobilization and differentiation of bone marrow stem cells for the treatment of fibrosis and liver regeneration

• Project/Area Number: 20790511
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Gastroenterology
• Research Institution: Tokai University
• Principal Investigator: HIGASHIYAMA Reiichi Tokai University, 医学部, 奨励研究員 (80459495)
• Project Period (FY): 2008 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2009: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 肝線維症 / 骨髄細胞 / コラーゲン / マトリックス分解酵素

Research Abstract

Overexpression of matrix metalloproteinase (MMP)-13 enhanced the migration of bone marrow (BM)-derived cells and their differentiation into sinusoidal cells in fibrotic liver. Expression of MMP-13/-9 mRNA and enzymatic activity of MMPs was detected in the regression of liver fibrosis in the model mice that produce MMP-13/-9 only by BM-derived cells. These results may suggest the therapeutic implications of MMPs in the repair and regeneration of fibrotic liver.

Research Products

• [Journal Article] Negligible contribution of bone marrow-derived cells to collagen production during hepatic fibrogenesis in mice. (2009)
  • Author(s): Reiichi Higashiyama, Tadashi Moro, Sachie Nakao, Kenichiro Mikami, Hiroshi Fukumitsu, Yoshitaka Ueda, Kazuo Ikeda, Eijiro Adachi, George Bou-Gharios, Isao Okazaki, Yutaka Inagaki
  • Journal Title: Gastroenterology 137 Pages: 1459-1466
  • Peer Reviewed
• [Journal Article] Negligible Contribution of Bone Marrow-Derived Cells to Collagen Production during Hepatic Fibrogenesis in Mice (2009)
  • Author(s): Reiichi Higashiyama
  • Journal Title: Gastroenterology 137 Pages: 1459-1466
  • Peer Reviewed
• [Journal Article] 細胞生物学講座骨髄細胞による肝線維化の病態形成 (2009)
  • Author(s): 稲垣豊
  • Journal Title: 細胞 42 Pages: 33-36
• [Journal Article] Glycyrrhizin and its metabolite inhibit Smad3-mediated type I collagen gene transcription and suppress experimental murine liver fibrosis. (2008)
  • Author(s): Tadashi Moro, Yoshihito Shimoyama, Miwa Kushida, Yun Yu Hong, Sachie Nakao, Reiichi Higashiyama, Yoshihiko Sugioka, Hideo Inoue, Isao Okazaki, Yutaka Inagaki
  • Journal Title: Life Sciences 83 Pages: 531-539
  • Peer Reviewed
• [Journal Article] Hepatocyte growth factor suppresses profibrogenic signal transduction via nuclear export of Smad3 with galectin-7. (2008)
  • Author(s): Yutaka Inagaki, Kiyoshi Higashi, Miwa Kushida, Yun Yu Hong, Sachie Nakao, Reiichi Higashiyama, Tadashi Moro, Johbu Itoh, Toshiyuki Mikami, Toru Kimura, Goshi Shiota, Ichiro Kuwabara, Isao Okazaki
  • Journal Title: Gastroenterology 134 Pages: 1180-1190
  • Peer Reviewed
• [Journal Article] Hepatocyte growth factor suppresses profibrogenic signal transduction via nuclear export of Smad3 with galectin-7 (2008)
  • Author(s): Yutaka Inagaki
  • Journal Title: Gastroenterology 134 Pages: 1180-1190
  • Peer Reviewed
• [Journal Article] Glycyrrhizin and its metabolite inhibit Smad3?mediated type I collagen gene transcription and suppress experimental murine liver fibrosis (2008)
  • Author(s): Tadashi Moro
  • Journal Title: Life Sciences 83 Pages: 531-539
  • Peer Reviewed
• [Journal Article] 肝線維化機序の解明で今何が問題になっているのか (2008)
  • Author(s): 稲垣豊
  • Journal Title: 肝胆膵 57 Pages: 187-192
• [Presentation] 骨髄細胞由来Matrix metalloproteinases (MMPs)による肝線維化改善機序の解明 (2010)
  • Author(s): 東山礼一
  • Organizer: 第9回再生医療学会総会
  • Place of Presentation: 広島
  • Year and Date: 2010-03-18
• [Presentation] Notchシグナルを介した肝線維化と再生の病態連繋 (2009)
  • Author(s): 三上健一郎
  • Organizer: 第23回肝類洞壁細胞研究会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2009-12-12
• [Presentation] A Comprehensive Analysis of Collagen Production and Degradation by Using Transgenic Dual Reporter Mice (2009)
  • Author(s): Yutaka Inagaki
  • Organizer: 60th Annual Meeting of the American Association for the Study of Liver Diseases
  • Place of Presentation: Boston, MA
  • Year and Date: 2009-11-02
• [Presentation] Role of Bone Marrow in Pathophysiology of Hepatic Fibrosis and Regeneration (2009)
  • Author(s): Reiichi Higashiyama
  • Organizer: Symposium VI "Molecular and Cellular Mechanisms of Tissue Remodeling and Fibrosis-Their Therapeutic Implications" Yokosuka Science Festa 2009
  • Place of Presentation: Yokosuka
  • Year and Date: 2009-06-06
• [Presentation] Cell-cell contacts differently regulate alpha-smooth muscle actin expression and collagen production in hepatic stellate cells (2009)
  • Author(s): Yoshitaka Ueda
  • Organizer: Yokosuka Science Festa 2009
  • Place of Presentation: Yokosuka
  • Year and Date: 2009-06-06
• [Presentation] Little contribution of epithelial-to-mesenchymal transition of biliary epithelial cells to the progression of experimental biliary fibrosis (2009)
  • Author(s): Sachie Nakao
  • Organizer: Yokosuka Science Festa 2009
  • Place of Presentation: Yokosuka
  • Year and Date: 2009-06-06
• [Presentation] A quantitative estimation system for fibrosis in non-alcoholic steatohepatitis by using transgenic collagen promoter/luciferase reporter (2009)
  • Author(s): Tadashi Moro
  • Organizer: Yokosuka Science Festa 2009
  • Place of Presentation: Yokosuka
  • Year and Date: 2009-06-05
• [Presentation] 胆汁うっ滞性肝線維症の発生・進展に上皮間葉移行は関与するか (2009)
  • Author(s): 稲垣豊
  • Organizer: 第45回日本肝臓学会総会
  • Place of Presentation: 神戸
  • Year and Date: 2009-06-04
• [Presentation] 皮膚創傷治癒ならびに線維化過程における骨髄由来細胞のコラーゲン合成への関与 (2009)
  • Author(s): 東山礼一
  • Organizer: 第108回日本皮膚科学会総会
  • Place of Presentation: 福岡
  • Year and Date: 2009-04-25
• [Presentation] 骨髄細胞由来Matrix metalloproteinases (MMPs)による肝線維化改善機序の解明 (2008)
  • Author(s): 東山礼一
  • Organizer: 第22回肝類洞壁細胞研究会ワークショップ2「肝再生と肝類洞壁細胞」
  • Place of Presentation: 久留米
  • Year and Date: 2008-11-29
• [Presentation] 骨髄細胞由来Matrix metalloproteinases(MMPs)による肝線維化改善機序の解明 (2008)
  • Author(s): 東山礼一
  • Organizer: 第22回肝類洞壁細胞研二究会、ワークショップ2「肝再生と肝類洞壁細胞」
  • Place of Presentation: 久留米
  • Year and Date: 2008-11-29
• [Presentation] Matrix metalloproteinases enhance migration of bone marrow-derived cells and contribute to the regression of experimental liver fibrosis. (2008)
  • Author(s): Reiichi Higashiyama
  • Organizer: 59th Annual Meeting of the American Association for the Study of Liver Diseases
  • Place of Presentation: San Francisco, CA
  • Year and Date: 2008-11-03
• [Presentation] Little contribution of bone marrow-derived cells to collagen production during hepatic fibrogenesis in mice. (2008)
  • Author(s): Yutaka Inagaki
  • Organizer: 59th Annual Meeting of the American Association for the Study of Liver Diseases
  • Place of Presentation: San Francisco, CA
  • Year and Date: 2008-11-03
• [Presentation] Little contribution of bone marrow-derived cells to collagen production during hepatic fibrogenesis in mice (2008)
  • Author(s): Yutaka Inagaki
  • Organizer: 59th Annual Meeting of the American Associa tion for the Study of Liver Diseases
  • Place of Presentation: San Francisco, CA
  • Year and Date: 2008-11-03
• [Presentation] Matrix metalloproteinases enhance migration of bone marrow-derived cells and contribute to the regression of experimental liver fibrosis (2008)
  • Author(s): Reiichi Higashiyama
  • Organizer: 59th Annual Meeting of the American Associa tion for the Study of Liver Diseases
  • Place of Presentation: San Francisco, CA
  • Year and Date: 2008-11-03
• [Presentation] 骨髄由来細胞の動員とMatrix metalloproteinases (MMPs)発現による肝線維化改善機序の解明 (2008)
  • Author(s): 東山礼一
  • Organizer: 第44回日本肝臓学会総会ワークショップ(8)「肝障害と修復に関する研究の展開」
  • Place of Presentation: 松山
  • Year and Date: 2008-06-06
• [Presentation] 骨髄由来細胞は肝線維化の進展に関与するか (2008)
  • Author(s): 稲垣豊
  • Organizer: 第44回日本肝臓学会総会
  • Place of Presentation: 松山
  • Year and Date: 2008-06-06
• [Presentation] 骨髄由来細胞の動員とMatrix metalloproteinases(MMPs)発現による肝線維化改善機序の解明 (2008)
  • Author(s): 東山礼一
  • Organizer: 第44回日本肝臓学会総会、ワークショップ(8)「肝障害と修復に関する研究の展開」
  • Place of Presentation: 松山
  • Year and Date: 2008-06-06
• [Presentation] 皮膚創傷治癒ならびに線維化過程における骨髄由来細胞のコラーゲン合成への関与 (2008)
  • Author(s): 東山礼一
  • Organizer: 第40回日本結合組織学会学術大会・第55回マトリックス研究会大会合同学術集会
  • Place of Presentation: 東京
  • Year and Date: 2008-05-30
• [Presentation] マウス部分胆管結紮モデルの確立と抗線維化薬の薬効評価への応用 (2008)
  • Author(s): 茂呂忠
  • Organizer: 第40回日本結合組織学会学術大会・第55回マトリックス研究会大会合同学術集会
  • Place of Presentation: 東京
  • Year and Date: 2008-05-29
• [Remarks]
  • URL: http://health.med.u-tokai.ac.jp/staff/inagaki/paper.html
• [Remarks]
  • URL: http://health.med.u-tokai.ac.jp/staff/inagaki/paper.html
• [Remarks]
  • URL: http://health.med.u-tokai.ac.jp/staff/inagaki/paper.html