Translational research of developing liver regeneration and antie agent derived from platelets

2010 Fiscal Year Final Research Report

• Project/Area Number: 20390350
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: University of Tsukuba
• Principal Investigator: OHKOHCHI Nobuhiro University of Tsukuba, 大学院・人間総合科学研究科, 教授 (40213673)
• Co-Investigator(Kenkyū-buntansha): MURATA Soichiro 筑波大学, 大学院・人間総合科学研究科, 講師 (40436275) ; KONDO Tadashi 筑波大学, 大学院・人間総合科学研究科, 准教授 (00375495) ; IKEDA Hiroshi 筑波大学, 大学院・数理物質科学研究科, 准教授 (50272167) ; FUKUNAGA Kiyoshi 筑波大学, 大学院・人間総合科学研究科, 講師 (20361339)
• Project Period (FY): 2008 – 2010
• Keywords: 肝臓外科学 / 肝再生

Research Abstract

The aim of this research is to develop new reagent for liver regeneration and anti-fibrosis. We clarified that human platelets directly deactivate human stellate cell by ATP and adenosine derived from human platelets. We also clarified that S1P from human platelets activate human liver sinusoidal endothelial cells to secrete IL-6 and proliferate hepatocytes. From these results, we will develop new reagents for treating severe liver diseases.

Research Products

• [Journal Article] Platelet administration via the portal vein promotes liver regeneration in rats after 70% hepatectomy. (2011)
  • Author(s): Matsuo R, Nakano Y, Ohkohchi N.
  • Journal Title: Annals of surgery. 235 Pages: 1-5
  • Peer Reviewed
• [Journal Article] Platelets PreventAcute Hepatitis Induced by Anti-Fas Antibody. (2011)
  • Author(s): Hisakura K, Murata S, Matsuo R, Paku S, Ikeda N, Kawasaki T, Kohno K, Myronovych A, Nakano Y, Ikeda O, Watanabe M, Ohkohchi N.
  • Journal Title: Journal of Gastroenterology and Hepatology. 26(2) Pages: 348-355
  • Peer Reviewed
• [Journal Article] Platelets play an important role in the recovery of liver dysfunction after hepatic resection. (2010)
  • Author(s): Ohkohchi N.
  • Journal Title: Annals of surgery. 252(4) Pages: 708-709
  • Peer Reviewed
• [Journal Article] Activation of human liver sinusoidal endothelial cell by human platelets induces hepatocyte proliferation. (2010)
  • Author(s): Kawasaki T, Murata S, Takahashi K, Nozaki R, Ohshiro Y, Ikeda N, Paku S, Myronovych A, Hisakura K, Fukunaga K, Oda T, Sasaki R, Ohkohchi N.
  • Journal Title: Journal of Hepatology. 53(4) Pages: 648-654
  • Peer Reviewed
• [Journal Article] Platelets Prevent Acute Liver Damageafter Extended Hepatectomy in Pigs. (2010)
  • Author(s): Hisakura K, Murata S, Fukunaga K, Myronovych A, Tadano S, Kawasaki T, Kohno K, Ikeda O, Paku S, Ikeda N, Nakano Y, Matsuo R, Kohno K, Kobayashi E, Saito T, Yasue H, Ohkohchi N.
  • Journal Title: Journal of hepato-biliary-pancreaticosurgery. 17(6) Pages: 855-864
  • Peer Reviewed
• [Journal Article] Platelet adhesion in the sinusoid caused hepatic injury by neutrophils after hepatic ischemia reperfusion. (2010)
  • Author(s): Paku S, Kondo T, Nakano Y, Murata S, Fukunaga K, oda T, Sasaki R, Ohkohchi N.
  • Journal Title: Platelets. 21(4) Pages: 282-288
  • Peer Reviewed
• [Journal Article] Prevention of leukocyte activation by the neutrophil elastase inhibitor, sivelestat, in the hepatic microcirculation after ischemia-reperfusion. (2009)
  • Author(s): Nakano Y, Kondo T, Matsuo R, Murata S, Fukunaga K, Ohkohchi N.
  • Journal Title: Journal of Surgical Research. 155(2) Pages: 311-317
  • Peer Reviewed
• [Journal Article] Platelets contribute to the reduction of liver fibrosis in mice. (2009)
  • Author(s): Watanabe M, Murata S, Hashimoto I, Nakano Y, Ikeda O, Aoyagi Y, Matsuo R, Fukunaga K, Yasue H, Ohkohchi N.
  • Journal Title: Journal of Gastroenterology and Hepatology. 24(1) Pages: 78-89
  • Peer Reviewed
• [Journal Article] Autonomic regulation of liver regeneration after partial hepatectomy in mice. (2009)
  • Author(s): Ikeda O, Ozaki M. Murata S, Matsuo R, Nakano Y, Watanabe M, Hisakura K, Myronovych A, Kawasaki T, Kohno K, Ohkohchi N.
  • Journal Title: Journal of Suegical Research. 152(2) Pages: 218-223
  • Peer Reviewed
• [Journal Article] Existence of Pink1 antisense RNAs in mouse and their localization. (2009)
  • Author(s): Chiba M, Kizawa H, Hiraiwa N, Ohkohchi N, Yasue H.
  • Journal Title: Cytogenetic and Genome Research. 126 Pages: 259-270
  • Peer Reviewed
• [Journal Article] Role of platelets on liver regeneration after 90% hepatectomy in mice. (2008)
  • Author(s): Myronovych A, Murata S, Chiba M, Matsuo R, Ikeda O, Watanabe M, Hisakura K, Nakano Y, Kohno K, Kawasaki T, Hashimoto I, Shibasaki Y, Yasue H, Ohkohchi N.
  • Journal Title: Journal of Hepatology. 49(3) Pages: 363-372
  • Peer Reviewed
• [Journal Article] Single Administration of Thrombopoietin Prevents Progression of Liver Fibrosis and Promotes Liver Regeneration after Partial Hepatectomy in Cirrhotic Rats. (2008)
  • Author(s): Murata S, Hashimoto I, Nakano Y, Myronovych A, Watanabe M, Ohkohchi N.
  • Journal Title: Annals of Surgery. 248 Pages: 821-828
  • Peer Reviewed
• [Journal Article] Platelet dynamics in the early phase of post-ischemic liver in vivo. (2008)
  • Author(s): Nakano Y, Kondo T, Matsuo R, Hashimoto I, Kawasaki T, Kohno K, Myronovych A, Tadano S, Hisakura K, Ikeda O, Watanabe M, Murata S, Ohkohchi N.
  • Journal Title: Journal of SurgicalResearch. 149(2) Pages: 192-198
  • Peer Reviewed
• [Journal Article] Platelets strongly induce hepatocyte proliferation with IGF-1 and HGF in vitro. (2008)
  • Author(s): Matsuo R, Ohkohchi N, Murata S, Ikeda O, Nakano Y, Watanabe M, Hisakura K, Myronovych A, Kubota T, Narimatsu H, Ozaki M.
  • Journal Title: Journal of Surgical Research. 145(2) Pages: 279-286
  • Peer Reviewed
• [Journal Article] Elevation and characteristics of Rab30 and S100a8/S100a9 expression in an early phase of liver regeneration in the mouse.
  • Author(s): Chiba M, Murata S, Myronovych A, Kohno K, Hiraiwa N, Nishibori M, Yasue H, Ohkohchi N.
  • Journal Title: International Journal of molecular medicine. Epub ahead of print.
  • Peer Reviewed
• [Presentation] 血小板による肝類洞内皮細胞からのIL-6分泌促進作用の検討 (2010)
  • Author(s): 川崎卓也、大河内信弘
  • Organizer: 第24回肝類洞壁細胞研究会学術集会
  • Place of Presentation: 福島
  • Year and Date: 2010-11-27
• [Presentation] 血小板による肝硬変の再生療法:基礎から臨床 (2010)
  • Author(s): 村田聡一郎、大河内信弘
  • Organizer: 第14回日本肝臓学会大会
  • Place of Presentation: 金沢
  • Year and Date: 2010-10-13
• [Presentation] 血小板による肝類洞内皮細胞からのIL-6分泌促進作用の検討 (2010)
  • Author(s): 川崎卓也、大河内信弘
  • Organizer: 第46回日本肝臓学会総会
  • Place of Presentation: 山形
  • Year and Date: 2010-05-27
• [Presentation] 肝再生促進・線維化抑制療法に濃厚血小板輸血療法を行った肝硬変の4症例 (2010)
  • Author(s): 大河内信弘
  • Organizer: 第46回日本肝臓学会総会
  • Place of Presentation: 山形
  • Year and Date: 2010-05-27
• [Presentation] Activation of human liver sinusoidal endothelial cell by human platelets induces hepatocyte proliferation. (2010)
  • Author(s): Kawasaki T, Ohkohchi N.
  • Organizer: The Internaional Liver CongressTM 2010 45th Annual Meeting of the European Association for the Study of the Liver.
  • Place of Presentation: Vienna, Austria
  • Year and Date: 2010-04-14
• [Presentation] 血小板は肝星細胞の活性化を抑制する (2010)
  • Author(s): 池田直哉、大河内信弘
  • Organizer: 第110回日本外科学会定期学術集会
  • Place of Presentation: 名古屋
  • Year and Date: 2010-04-08
• [Presentation] 血小板は肝類洞内皮細胞を活性化しその結果肝細胞増殖を促進する(ヒト細胞を用いたin vitroでのメカニズムの検討) (2010)
  • Author(s): 川崎卓也、大河内信弘
  • Organizer: 第110回日本外科学会定期学術集会
  • Place of Presentation: 名古屋
  • Year and Date: 2010-04-08
• [Presentation] Platelet Infusion Therapy Promotes Liver Regeneration After An Extended Hepatectomy in Rats. (2009)
  • Author(s): R Matsuo, N Ohkohchi.
  • Organizer: EASL.
  • Place of Presentation: Copenhagen
  • Year and Date: 20090422-20090426
• [Presentation] Platelets keep human hepatic stellate cell in stable state by the ERK signaling pathway. (2009)
  • Author(s): N Ikeda, N Ohkohchi.
  • Organizer: International Symposium on Cellular Singaling~principles and functions~.
  • Place of Presentation: tsukuba.
  • Year and Date: 2009-11-18
• [Presentation] 血小板による肝硬変治療の臨床研究の経過報告 (2009)
  • Author(s): 大河内信弘
  • Organizer: 第11回日本肝臓医生物学研究会
  • Place of Presentation: 東京
  • Year and Date: 2009-10-17
• [Presentation] 血小板は肝星細胞活性を抑制する (2009)
  • Author(s): 池田直哉, 大河内信弘
  • Organizer: 第13回日本肝臓学会大会
  • Place of Presentation: 京都
  • Year and Date: 2009-10-14
• [Presentation] 脾摘による慢性肝炎モデルの肝線維化抑制効果と過大肝切除モデルの肝障害抑制効果の検討 (2009)
  • Author(s): 村田聡一郎, 大河内信弘
  • Organizer: 第64回日本消化器外科学会総会
  • Place of Presentation: 大阪
  • Year and Date: 2009-07-16
• [Presentation] 血小板による難治性肝疾患治療法開発のためのプロジェクトX (2009)
  • Author(s): 大河内信弘
  • Organizer: 第21回肝胆膵外科学会学術集会
  • Place of Presentation: 名古屋
  • Year and Date: 2009-06-10
• [Presentation] 血小板は肝星細胞のαSMA発現を抑制する (2009)
  • Author(s): 池田直哉, 大河内信弘
  • Organizer: 第45回日本肝臓学会総会
  • Place of Presentation: 神戸
  • Year and Date: 2009-06-04
• [Presentation] 血小板は肝類洞内皮細胞を活性化し肝細胞を増殖させる (2009)
  • Author(s): 川崎卓也, 大河内信弘
  • Organizer: 第45回日本肝臓学会総会
  • Place of Presentation: 神戸
  • Year and Date: 2009-06-04
• [Patent(Industrial Property Rights)] 肝線維化抑制剤 (2011)
  • Inventor(s): 大河内信弘, 村田聡一郎, 渡辺基信, 中野順隆, 橋本育佳
  • Industrial Property Rights Holder: 国立大学法人筑波大学
  • Industrial Property Number: 特許,特許第4696247号
  • Acquisition Date: 2011-03-11