Analysis of characteristics of cellular subfractions in adipose tissue-derived stromal cells for development of liver repair/regenerative therapy

• Project/Area Number: 26460995
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Kanazawa University
• Principal Investigator: Sakai Yoshio 金沢大学, 医学系, 准教授 (80401925)
• Research Collaborator: SEKI Akihiro 金沢大学, 附属病院 ; YAMATO Masatoshi 金沢大学, 医薬保健学総合研究科恒常性制御学, 大学院生 ; NASTI Alessandro 金沢大学, 医薬保健学総合研究科恒常性制御学, 大学院生 ; YOSHIDA Keiko 金沢大学, 技術補佐員
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 肝臓学 / 肝再生 / 脂肪組織由来間質細胞 / 肝再生療法

Outline of Final Research Achievements

In this study, we analyzed the cellular fractions of murine uncultured adipose tissue derived stromal cells and assessed their characteristics. In addition, we investigated their effect on the liver disease condition using murine liver disease models. We found that the 10-20% of uncultured adipose tissue-derived stromal cells expressed CD45 antigen. CD45+ cells were disclosed to be characteristics of M2 phenotype macrophage in view of surface antigen analysis as well as gene expression analysis. Administration of the entire ulcutred adipose tissue derived stromal cells and their CD45+ fraction were effective to acute murine hepatitis. Thus, these results indicated that the relative importance of CD45+ cellular fraction of the uncultured adipose tissue derived stromal cells in the context of their immunomodulatory effect.

Research Products

• [Journal Article] Phase I clinical study of liver regenerative therapy for cirrhosis by intrahepatic arterial infusion of freshly isolated autologous adipose tissue-derived stromal/stem (regenerative) cell. (2017)
  • Author(s): Sakai Y, Takamura M, Seki A, Sunagozaka H, Terashima T, Komura T, Yamato M, Miyazawa M, Kawaguchi K, Nasti A, Mochida H, Usui S, Otani N, Ochiya T, Wada T, Honda M, Kaneko S.
  • Journal Title: Regenerative Therapy Volume: 6C Pages: 52-64
  • Peer Reviewed / Open Access
• [Journal Article] Branched-chain amino acids prevent hepatic fibrosis and development of hepatocellular carcinoma in a non-alcoholic steatohepatitis mouse model. (2017)
  • Author(s): K Takegoshi, M Honda, H Okada, R Takabatake, N Matsuzawa-Nagata, JS Campbell, M Nishikawa, T Shimakami, T Shirasaki, Y Sakai, T Yamashita, T Takamura, T Tanaka, S Kaneko.
  • Journal Title: Oncotarget Volume: 印刷中 Issue: 11 Pages: 18191-18205
  • DOI: 10.18632/oncotarget.15304
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Adipose-derived regenerative cells exert beneficial effects on systemic responses following myocardial ischemia/reperfusion. (2016)
  • Author(s): Takamura M, Usui S, Inoue O, Ootsuji H, Takashima SI, Nomura A, Kato T, Murai H, Furusho H, Sakai Y, Kaneko S.
  • Journal Title: Cardiol J Volume: 23 Issue: 6 Pages: 685-693
  • DOI: 10.5603/cj.a2016.0061
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Response to chemotherapy improved hepatic reserve for patients with hepatocellular carcinoma and Child-Pugh B cirrhosis. (2016)
  • Author(s): Terashima T, Yamashita T, Arai K, Kawaguchi K, Kitamura K, Yamashita T, Sakai Y, Mizukoshi E, Honda M, Kaneko S.
  • Journal Title: Cancer Sci. Volume: 107(9) Issue: 9 Pages: 1263-1269
  • DOI: 10.1111/cas.12992
  • NAID: 120005851362
  • Peer Reviewed / Open Access
• [Journal Article] Jagged1 DNA Copy Number Variation Is Associated with Poor Outcome in Liver Cancer. (2016)
  • Author(s): Kawaguchi K, Honda M, Yamashita T, Okada H, Shirasaki T, Nishikawa M, Nio K, Arai K, Sakai Y, Yamashita T, Mizukoshi E, Kaneko S.
  • Journal Title: Am J Pathol. Volume: 186(8) Issue: 8 Pages: 2055-2067
  • DOI: 10.1016/j.ajpath.2016.04.011
  • NAID: 120005899105
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Hepatitis B Virus (HBV) Core-Related Antigen During Nucleos(t)ide Analog Therapy Is Related to Intra-hepatic HBV Replication and Development of Hepatocellular Carcinoma. (2016)
  • Author(s): Honda M, Shirasaki T, Terashima T, Kawaguchi K, Nakamura M, Oishi N, Wang X, Shimakami T, Okada H, Arai K, Yamashita T, Sakai Y, Yamashita T, Mizukoshi E, Kaneko S.
  • Journal Title: J Infect Dis Volume: 213 Issue: 7 Pages: 1096-1106
  • DOI: 10.1093/infdis/jiv572
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Inhibition of microRNA-214 ameliorates hepatic fibrosis and tumor incidence in platelet-derived growth factor C transgenic mice. (2015)
  • Author(s): Okada H, Honda M, Campbell JS, Takegoshi K, Sakai Y, Yamashita T, Shirasaki T, Takabatake R, Nakamura M, Tanaka T, Kaneko S.
  • Journal Title: Cancer Sci. Volume: 106 Pages: 1143-1152
  • NAID: 120005830608
  • Peer Reviewed
• [Journal Article] Inflammatory Features of Pancreatic Cancer Highlighted byMonocytes/Macrophages and CD4+ T cells with Clinical Impact. (2015)
  • Author(s): Komura T, Sakai Y, Harada K, Kawaguchi K, Takabatake H, Kitagawa H, Wada T, Honda M, Ohta T, Nakanuma Y, Kaneko S.
  • Journal Title: Cancer Sci. Volume: 106(6) Issue: 6 Pages: 672-86
  • DOI: 10.1111/cas.12663
  • Peer Reviewed / Open Access
• [Journal Article] The efficacy of Continuous Plasma Diafiltraion Therapy in critical Patients with Acute Liver Failure. (2014)
  • Author(s): Komura T, Taniguchi T, Sakai Y, Yamashita T, Mizukoshi E, Noda T, Okajima M, Kaneko S.
  • Journal Title: J Gastroenterol Hepatol Volume: 29 Issue: 4 Pages: 782-786
  • DOI: 10.1111/jgh.12440
  • Peer Reviewed
• [Presentation] 医師主導治験を目指した自己脂肪組織由来再生（幹）細胞による肝硬変再生療法実用化研究 (2017)
  • Author(s): 酒井佳夫
  • Organizer: 再生医療サミット IN OKINAWA 2017
  • Place of Presentation: 沖縄
  • Invited
• [Presentation] 体性幹細胞を含む自己脂肪組織由来間質細胞による肝硬変再生療法実用化開発 ～ 非臨床・臨床研究から治験準備にむけて (2017)
  • Author(s): 酒井佳夫
  • Organizer: 第2回再生医療セミナー
  • Place of Presentation: 金沢
  • Invited
• [Presentation] 自己脂肪組織由来間質細胞の経肝動脈投与による肝硬変療法臨床開発 (2016)
  • Author(s): 酒井佳夫、関 晃裕、金子周一
  • Organizer: 第102回日本消化器病学会総会
  • Place of Presentation: 東京
• [Presentation] 肝硬変に対する自己脂肪組織由来再生（幹）細胞を用いた安全性臨床試験 (2016)
  • Author(s): 酒井佳夫、関 晃裕、金子周一
  • Organizer: JDDW 2016
  • Place of Presentation: 神戸
• [Presentation] linical study of liver regenerative therapy of cirrhosis using autologous adipose tissue derived stromal cells and the characterization of the obtained stromal cells (2016)
  • Author(s): Y. Sakai, A. Seki, H. Sunagozaka, T. Terashima, K. Kawaguchi, G.B. Buffa, M. Honda, S. Kaneko
  • Organizer: AASLD, The Liver Meeting 2016
  • Place of Presentation: Boston
  • Int'l Joint Research
• [Presentation] 肝硬変に対する自己脂肪組織由来間質細胞の経肝動脈投与による肝再生療法の臨床試験 (2015)
  • Author(s): 酒井佳夫、関晃裕、砂子阪 肇、高村雅之、金子周一
  • Organizer: 第41回日本肝臓学会西部会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2015-12-03
• [Presentation] Adipose tissue-derived stromal cells preventatively suppressed pathological progression of murine non-alcoholic steatohepatitis model. (2015)
  • Author(s): Masatoshi Yamato, Yoshio Sakai, Hatsune Mochida, Akihiro Seki, Kosuke Ishida, Masao Honda, Shuichi Kaneko.
  • Organizer: AASLD The Liver Meeting 2015
  • Place of Presentation: Moscone West Convention Center, San Francisco
  • Year and Date: 2015-11-15
  • Int'l Joint Research
• [Presentation] CD45+ fraction in murine adipose tissue-derived stromal cells is therapeutical to Concanavalin A-induced murine acute hepatitis model. (2015)
  • Author(s): Akihiro Seki, Yoshio Sakai, Masatoshi Yamato, Kosuke Ishida, Hisashi Takabatake, Alessandro Nasti, Masao Honda, Shuichi Kaneko.
  • Organizer: AASLD The Liver Meeting 2015
  • Place of Presentation: Moscone West Convention Center, San Francisco
  • Year and Date: 2015-11-14
  • Int'l Joint Research
• [Presentation] 肝疾患マウスモデルを用いた脂肪組織由来間葉系幹細胞による肝再生治療効果と機序の検討 (2015)
  • Author(s): 酒井佳夫、関 晃裕、金子 周一
  • Organizer: 第51回日本肝臓学会総会
  • Place of Presentation: ホテル日航熊本
  • Year and Date: 2015-05-22
• [Presentation] 前臨床非アルコール性肝炎肝硬変マウスモデルに対する脂肪組織由来間質細胞投与による肝修復再生治療効果の検討 (2014)
  • Author(s): 酒井佳夫、関 晃裕、東元真実、吉田佳子、ナスティ・アレッサンドロ、小村卓也、本多政夫、金子周一
  • Organizer: 第50回日本肝臓学会総会
  • Place of Presentation: ホテルニューオータニー(東京・千代田区）
  • Year and Date: 2014-05-29
• [Book] 再生医療等製品の開発と実用化展望 (2016)
  • Author(s): 酒井佳夫、金子周一
  • Total Pages: 10
  • Publisher: シーエムシー出版刊