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

• 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
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥19,890,000 (Direct Cost: ¥15,300,000、Indirect Cost: ¥4,590,000); Fiscal Year 2010: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2009: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2008: ¥12,480,000 (Direct Cost: ¥9,600,000、Indirect Cost: ¥2,880,000)
• Keywords: 肝臓外科学 / 肝再生 / 肝臓 / 血小板 / 肝線維化 / 治療法

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
  • NAID: 120007137327
  • 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] 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 Volume: 235 Pages: 1-5
  • NAID: 120007137327
  • Peer Reviewed
• [Journal Article] Platelets Prevent Acute 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 Volume: 26(2) Pages: 348-355
  • Peer Reviewed
• [Journal Article] Elevation and characteristics of Rab30 and S100a8/S100a9 expression inan early phase of liver regeneration in the mouse. (2011)
  • 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. Volume: (Epub ahead of print)
  • 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
  • NAID: 120007137912
  • 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
  • NAID: 120007130823
  • 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 Volume: 252(2) 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. Volume: 53(4) Pages: 648-654
  • NAID: 120007137912
  • Peer Reviewed
• [Journal Article] Platelets Prevent Acute Liver Damage after Extended Hepatectomy inPigs. (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-pancreatico surgery. Volume: 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 Volume: 21(4) Pages: 282-288
  • NAID: 120007130823
  • Peer Reviewed
• [Journal Article] Platelet adhesion in the sinusoid caused hepatic injury by neutrophils after hepatic ischemia reperfusion (2010)
  • Author(s): S Paku, T Kondo, Y Nakano, S Murata, K Fukunaga, T Oda, R Sasaki, N Ohkohchi
  • Journal Title: Platelets (E pub)
  • NAID: 120007130823
  • Peer Reviewed
• [Journal Article] Platelets Prevent Acute Liver Damage after Extended Hepatectomy in Pigs (2010)
  • Author(s): K Hisakura, S Murata, K Fukunaga, A Myronovych, S Tadano, T Kawasaki, K Kohno, O Ikeda, S Paku, N Ikeda, Y Nakano, R Matsuo, K Konno, E Kobayashi, T Saito, H Yasue, N Ohkohchi
  • Journal Title: Journal of hepato biliary pancreatico surgery (印刷中)
  • NAID: 10027664195
  • Peer Reviewed
• [Journal Article] Platelets Prevent Acute Hepatitis Induced by Anti-Fas Antibody (2010)
  • Author(s): K Hisakura, S Murata, R Matsuo, S Paku, N Ikeda, T Kawasaki, K Kohno, A Myronovych, Y Nakno, O Ikeda, M Watanabe, N Ohkohchi
  • Journal Title: Journal of Gastroenterology and Hepatology (印刷中)
  • 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] Platelets contribute to the reduction of liver fibrosis in mice (2009)
  • Author(s): M Watanabe, S Murata, I Hashimoto, Y Nakano, O Ikeda, Y Aoyagi, R Matsuo, K Fukunaga, H Yasue, N Ohkohchi
  • Journal Title: Journal of Gastroenterology and Hepatology 24(1) Pages: 78-89
  • Peer Reviewed
• [Journal Article] Autonomic regulation of liver regeneration ofter partial hepatectomy in mice (2009)
  • Author(s): O Ikeda, M Ozaki, R Matsuo, Y Nakano, M Watanabe, K Hisakura, A Myronovych, T Kawasaki, K Kohno, N Ohkohchi
  • Journal Title: Journal of Surgical Reseach 152(2) Pages: 218-223
  • 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
  • NAID: 120007138589
  • 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
  • NAID: 120007138815
  • Peer Reviewed
• [Journal Article] Single Administration of Thrombopoietin Prevents Progression of Liver Fibrosis and Promotes Liver Regeneration after P artial Hepatectomv 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] 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] 脂肪酸合成酵素阻害剤セルレニンはマウス大腸癌肝転移を抑制する (2010)
  • Author(s): 村田聡一郎、川崎卓也、池田直哉、大城幸雄、高橋一広、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
• [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、村田聡一郎、高橋一広、大城幸雄、川崎卓也、Andriy Myronovych、大河内信弘
  • Organizer: 第110回日本外科学会定畑学術集会
  • Place of Presentation: 名古屋
• [Presentation] 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, IkedaN, Pak S, Myronovych A, Hisakura K, Fukunaga K, Oda T, Sasaki R, Ohkohchi N.
  • Organizer: The Internaional Liver Congress<TM> 2010 45^<th> Annual Meeting of the European Association for the Study of the Liver
  • Place of Presentation: Vienna, Austria
• [Presentation] 3種類の肝切除モデルを用いた血小板による肝再生促進効果の検討 (2010)
  • Author(s): 村田聡一郎、Andriy Myronovych、中野順隆、大河内信弘
  • Organizer: 第22回日本肝胆膵外科学会・学術集会
  • Place of Presentation: 仙台
• [Presentation] 肝虚血再灌流障害におけるKupffer細胞と好中球動態のin vivoイメージングシステムの開発 (2010)
  • Author(s): 朴秀吉、近藤匡、中野順隆、村田聡一郎、福永潔、大河内信弘
  • Organizer: 第46回日本肝臓学会総会
  • Place of Presentation: 山形
• [Presentation] 脂肪酸合成酵素阻害剤による大腸癌肝転移抑制効果の検討 (2010)
  • Author(s): 村田聡一郎、柳澤和彦、大河内信弘
  • Organizer: 第65回日本大腸肛門病学会学術集会
  • Place of Presentation: 浜松
• [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
• [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
• [Presentation] 血小板を用いた肝硬変に対する再生治療の開発:基礎と臨床の橋渡し研究 (2009)
  • Author(s): 村田聡一郎, 中野順隆, 渡辺基信
  • Organizer: 第109回日本外科学会定期学術集会
  • Place of Presentation: 福岡
• [Presentation] 好中球エラスターゼ阻害剤による肝虚血再潅流障害防止における血小板動態の解明 (2009)
  • Author(s): 朴秀吉, 近藤匡, 中野順隆, 福永潔, 大河内信弘
  • Organizer: 第109回日本外科学会定期学術集会
  • Place of Presentation: 福岡
• [Presentation] New therapy for promotion of regeneration and resolution of fibrosis in the liver by platelets : basic research to clinical trial (2009)
  • Author(s): 村田聡一郎, 大河内信弘, 渡辺基信, 中野順隆, A Myronovych, 福永潔
  • Organizer: 第36回日本臓器保存生物医学会定期学術集会
  • Place of Presentation: 岡山
• [Presentation] Platelet Infusion Therapy Promotes Liver Regeneration After An Extended Hepatectomy in Rats. (2009)
  • Author(s): R Matsuo, Y Nakano, S Murata, N Ohkohchi
  • Organizer: 2009 EASL
  • Place of Presentation: Copenhagen(デンマーク)
• [Presentation] 好中球エラスターゼ阻害剤投与による虚血再潅流後の肝における血小板動態の解析 (2009)
  • Author(s): 朴秀吉, 近藤匡, 中野順隆, 池田直哉, 川崎卓也, 久倉勝治, アンドリーミロノヴィチ, 村田聡一郎, 福永潔, 大河内信弘
  • Organizer: 第45回日本肝臓学会総会
  • Place of Presentation: 神戸
• [Presentation] Platelets keep human hepatic stellate cell in stable state by the ERK signaling pathway (2009)
  • Author(s): 池田直哉, 村田聡一郎, K Takahashi, Y Ohshiro, 川崎卓也, A Myronovych, 大河内信弘
  • Organizer: International Symposium on Cellular Singaling～principles and functions～
  • Place of Presentation: つくば
• [Presentation] 血小板による肝硬変の再生療法の開発:基礎と臨床のBridge研究 (2008)
  • Author(s): 村田聡一郎、橋本育佳、大河内信弘
  • Organizer: 第12回日本肝臓学会大会
  • Place of Presentation: 東京、グランドプリンスホテル新高輪
  • Year and Date: 2008-10-01
• [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
  • Acquisition Date: 2011-03-11