Basic studies into development of novel preventive and regenerative therapy for hepatocarcinogenic cirrhosis using bone marrow-derived cells having redox-regulatory capacity

2013 Fiscal Year Final Research Report

• Project/Area Number: 24790703
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology
• Research Institution: Yamaguchi University
• Principal Investigator: TAKAMI Taro 山口大学, 医学(系)研究科(研究院), 講師 (60511251)
• Research Collaborator: QUINTANILHA Luiz Fernand 山口大学, 大学院医学系研究科, 助教研究者
• Project Period (FY): 2012-04-01 – 2014-03-31
• Keywords: 肝硬変症 / 肝再生療法 / 骨髄細胞 / 酸化ストレス

Research Abstract

We previously developed autologous bone marrow cell infusion (ABMi) therapy, which is a method of liver regeneration for liver cirrhotic patients using non-cultured autologous whole bone marrow cells, and reported the efficacy and safety of this approach. This ABMi therapy was officially approved as an "Advanced Medical Technology B" in Japan. We also reported that frequent bone marrow cell infusion contributed to suppressed tumor initiation during hepatocarcinogenesis. In these studies, we confirmed that hepatocytes co-cultured with bone marrow derived mesenchymal stem cells (MSCs) had lower levels of oxidative stress, and that cirrhotic mice treated with MSCs showed lower levels of liver fibrosis, higher serum antioxidant activity, and lower levels of hepatic malondialdehyde content. These results strongly indicate that cultured BMCs are a stem cell source in liver regeneration therapy for cirrhotic patients.

Research Products

• [Journal Article] Canine mesenchymal stem cells show antioxidant properties against thioacetamide-induced liver injury in vitro and in vivo (2013)
  • Author(s): Quintanilha LF, Takami T, Hirose Y, Fujisawa K, Murata Y, Yamamoto N, Goldenberg RC, Terai S, Sakaida I
  • Journal Title: Hepatol Res. Volume: [Epub ahead of print]
  • Peer Reviewed
• [Journal Article] Improvement of liver fibrosis by infusion of cultured cells derived from human bone marrow (2013)
  • Author(s): Tanimoto H, Terai S, Takami T, Murata Y, Fujisawa K, Yamamoto N, Sakaida I
  • Journal Title: Cell Tissue Res. Volume: [Epub ahead of print]
  • Peer Reviewed
• [Journal Article] Bone-marrow-derived cells cultured in serum-free medium reduce liver fibrosis and improve liver function in carbon-tetrachloride-treated cirrhotic mice (2013)
  • Author(s): Iwamoto T, Terai S, Hisanaga T, Takami T, Yamamoto N, Watanabe S, Sakaida I
  • Journal Title: Cell Tissue Res. Volume: 351(3) Pages: 487-495
  • Peer Reviewed
• [Journal Article] Advanced therapies using autologous bone marrow cells for chronic liver disease (2012)
  • Author(s): Takami T, Terai S, Sakaida I
  • Journal Title: Discov Med. Volume: 14(74) Pages: 7-12
  • Peer Reviewed
• [Journal Article] Stem cell therapy in chronic liver disease (2012)
  • Author(s): Takami T, Terai S, Sakaida I
  • Journal Title: Curr Opin Gastroenterol. Volume: 28(3) Pages: 203-208
  • Peer Reviewed
• [Journal Article] Autologous bone marrow cell infusions suppress tumor initiation in hepatocarcinogenic mice with livercirrhosis (2012)
  • Author(s): Maeda M, Takami T, Terai S, Sakaida I
  • Journal Title: J Gastroenterol Hepatol. Volume: 27(Suppl2) Pages: 104-111
  • Peer Reviewed
• [Journal Article] Timeline for development of autologous bone marrow infusion (ABMi) therapy and perspective for future stem cell therapy (2012)
  • Author(s): Terai S, Tanimoto H, Maeda M, Zaitsu J, Hisanaga T, Iwamoto T, Fujisawa K, Mizunaga Y, Matsumoto T, Urata Y, Marumoto Y, Hidaka I, Ishikawa T, Yokoyama Y, Aoyama K, Tsuchiya M, Takami T, Omori K, Yamamoto N, Segawa M, Uchida K, Yamasaki T, Okita K, Sakaida I
  • Journal Title: J Gastroenterol. Volume: 47(5) Pages: 491-497
  • Peer Reviewed
• [Presentation] Liver regeneration therapy for liver cirrhosis using cultured autologous bone marrow-derived mesenchymal stem cells with stabilization of redox homeostasis (2014)
  • Author(s): Takami T, Terai S, Sakaida I
  • Organizer: Choshu International Liver Symposium 2014
  • Place of Presentation: Ube, Yamaguchi, Japan (ANA Crowne Plaza Hotel UBE)
  • Year and Date: 2014-01-25
• [Presentation] Basic studies for a less invasive liver regeneration therapy for liver cirrhosis using cultured autologous bone marrow-derived mesenchymal stem cells with stabilization of redox homeostasis (2013)
  • Author(s): Takami T, Terai S, Quintanilha LF, Fujisawa K, Yamamoto N, Sakaida I
  • Organizer: The liver meeting 2013, AASLD
  • Place of Presentation: Washington D.C., USA.
  • Year and Date: 20131031-1105
• [Presentation] The development of a less-invasive liver regeneration therapy using cultured bone marrow derived cells for cirrhotic patients (2013)
  • Author(s): Takami T, Terai S, Sakaida I
  • Organizer: JDDW2013
  • Place of Presentation: Shinagawa, Tokyo, Japan (Grand Prince Hotel New Takanawa, Pamir)
  • Year and Date: 20131009-12
• [Presentation] Basic studies for a less invasive liver regeneration therapy for liver cirrhosis using cultured autologous bone marrow-derived mesenchymal stem cells with stabilization of redox homeostasis (2013)
  • Author(s): Takami T, Terai S, Quintanilha LF, Fujisawa K, Yamamoto N, Sakaida I
  • Organizer: The 20th Annual Meeting of the Japanese Society for the Research of Hepatic Cells (20th JSRH)
  • Place of Presentation: Osaka, Japan( Osaka International ConventionCenter)
  • Year and Date: 20130926-27
• [Presentation] The development of a less-invasive liver regeneration therapy using cultured bone marrow derived cells for cirrhotic patient (2013)
  • Author(s): Takami T, Terai S, Sakaida I
  • Organizer: 2nd The International Conference on Gastroenterology & Urology
  • Place of Presentation: Northbrook, IL, USA.
  • Year and Date: 20130610-12
• [Presentation] Basic studies using human and canine bone marrow derived mesenchymal stem cells for the development of a less invasive liver regeneration therapy for liver cirrhotic patients (2013)
  • Author(s): Takami T, Terai S, Quintanilha LF, Tanimoto H, Murata Y, Fujisawa K, Yamamoto N, Sakaida I
  • Organizer: The 11th Annual meeting of ISSCR
  • Place of Presentation: Boston, MA, USA.
  • Year and Date: 20130112-15
• [Presentation] 自己骨髄細胞による肝臓再生療法の取り組み (2013)
  • Author(s): 高見 太郎、寺井崇二、坂井田 功
  • Organizer: 第40回日本肝臓学会西部会
  • Place of Presentation: (長良川国際会議場、岐阜市、岐阜)
  • Year and Date: 2013-12-06
• [Presentation] ヒト骨髄由来および脂肪組織由来間葉系幹細胞における組織因子および IL-8の発現検討 (2013)
  • Author(s): 高見太郎、寺井崇二、村田泰彦、坂井田功
  • Organizer: 第49回日本肝臓学会総会
  • Place of Presentation: (京王プラザホテル、新宿区、東京都)
  • Year and Date: 2013-06-06
• [Presentation] 肝再生修復療法としての培養ヒト骨髄間葉系細胞投与療法のメカニズム解析 (2013)
  • Author(s): 高見 太郎、寺井 崇二、村田泰彦、廣瀬 恵一、藤澤 浩一、山本 直樹、坂井田 功
  • Organizer: 第49回日本肝臓学会総会
  • Place of Presentation: (京王プラザホテル、新宿区、東京都)
  • Year and Date: 2013-06-06
• [Presentation] 肝再生修復療法としての培養ヒト骨髄間葉系細胞投与療法のメカニズム解析 (2013)
  • Author(s): 高見 太郎、寺井 崇二、村田泰彦、Quintanilha LF、廣瀬 恵一、藤澤 浩一、山本 直樹、坂井田 功
  • Organizer: 第12回日本再生医療学会総会
  • Place of Presentation: (パシフィコ横浜、横浜市、神奈川県)
  • Year and Date: 2013-03-21
• [Presentation] 自己骨髄細胞による肝硬変に対する再生修復療法の現状と展望 (2013)
  • Author(s): 高見 太郎、寺井 崇二、坂井田 功
  • Organizer: 第32回日本画像医学会
  • Place of Presentation: (ホテルメトロポリタン東京、千代田区、東京都)
  • Year and Date: 2013-02-23
• [Presentation] The development of a less-invasive liver regeneration therapy using cultured bone marrow derived cells for cirrhotic patients (2013)
  • Author(s): Takami T, Terai S, Murata Y, Quintanilha LF, Hirose Y, Fujisawa K, Yamamoto N, Sakaida I
  • Organizer: Choshu International Liver Symposium 2013
  • Place of Presentation: Ube, Yamaguchi, Japan (ANA Crowne Plaza Hotel UBE)
  • Year and Date: 2013-02-09
• [Book] Liver Resident Stem Cell (2012)
  • Author(s): Takiya CM, Paredes BD, Quintanilha LF, Dias GS, Pinheiro LA, Takami T, Terai S, Sakaida I, Regina SG
  • Total Pages: 177-203
  • Publisher: ELSEVIER