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2020 年度 実施状況報告書

Study of liver restorative therapy for a murine nonalcoholic steatohepatitis model by the administration of immune-suppressive fractions of autologous adipose tissue-derived stromal cells

研究課題

研究課題/領域番号 20K08327
研究機関金沢大学

研究代表者

Nasti Alessandro  金沢大学, 医学系, 博士研究員 (20830871)

研究分担者 関 晃裕  金沢大学, 医学系, 特任助教 (00733859)
酒井 佳夫  金沢大学, 医学系, 准教授 (80401925)
研究期間 (年度) 2020-04-01 – 2024-03-31
キーワードNASH / uncultured ADSCs
研究実績の概要

NASH is a major cause of chronic liver disease, and effective treatment should be developed. Freshly isolated uncultured adipose tissue-derived stromal cells (u-ADSCs) are advantageous, they have pluripotent and immunomodulatory capabilities. We compared characteristics of u-ADSCs from wild mice and from mice affected by NASH. In the context of surface antigens and gene expression profile features, u-ADSCs from wild mice and u-ADSCs from NASH mice, fed with NASH diet for 4 weeks (NASH-4w) or 12 weeks (NASH-12w), did not show marked differences, except for u-ADSCs isolated from NASH-4w mice which showed a slight increase in frequency of CD11b, CD45 and CD44 surface markers, indicating a possible presence of WBCs, as well as an enhanced cell cycle related gene expression character.

現在までの達成度 (区分)
現在までの達成度 (区分)

2: おおむね順調に進展している

理由

Regarding the research progression in FY2020, all experiments and analyses proceeded steadily. We performed as planned, a full flow cytometry and DNA microarray analyses of uncultured adipose tissue-derived stromal cells (u-ADSCs) and of NASH mice-derived u-ADSCs; regarding the flow cytometry analysis we investigated the expression of the following surface antigens: CD11b, CD73, CD31, CD34, CD90, CD29. CD45, CD105, CD44, Ly6c and Gr-1.

今後の研究の推進方策

Following the characterization of uncultured adipose tissue-derived stromal cells (u-ADSCs), we will proceed with the investigation of the effect of wild type u-ADSCs treatment of NASH-cirrhotic mice by evaluating the hepatic inflammatory cells infiltration as well as extent of fibrosis in livers. We are planning to evaluate the hepatic inflammatory cells infiltration using immunohistochemical and flow cytometry analyses, furthermore fibrosis quantification will be performed by staining liver tissue of mice treated with u-ADSCs.

次年度使用額が生じた理由

A part of the funds were not used in FY2020 due to the Coronavirus pandemic, funds were not used for the planned travelling expenses and conference fees (national and international conferences). All other expenses in FY2020 proceeded as planned. In FY2021, as well, it is expected the use of funds as planned in the original research plan.

  • 研究成果

    (5件)

すべて 2020

すべて 雑誌論文 (1件) (うち国際共著 1件、 オープンアクセス 1件) 学会発表 (4件) (うち国際学会 4件)

  • [雑誌論文] Regenerative Therapy for Liver Cirrhosis Based on Intrahepatic Arterial Infusion of Autologous Subcutaneous Adipose Tissue-Derived Regenerative (Stem) Cells: Protocol for a Confirmatory Multicenter Uncontrolled Clinical Trial2020

    • 著者名/発表者名
      Sakai Yoshi, Fukunishi Shinya, Takamura Masayuki, et al
    • 雑誌名

      JMIR Research Protocols

      巻: 9 ページ: e17904~e17904

    • DOI

      10.2196/17904

    • オープンアクセス / 国際共著
  • [学会発表] Therapy with adipose tissue-derived mesenchymal stromal/stem cells for NASH mice enhance the activation of Notch signaling and alleviate apoptosis in hepatocytes.2020

    • 著者名/発表者名
      Kosuke Ishida, Yoshio Sakai, Akihiro Seki, Kazunori Kawaguchi, Alessandro Nasti, Hiiro Inui, Takashi Wada, Shuichi Kaneko
    • 学会等名
      AASLD, The Liver Meeting 2020
    • 国際学会
  • [学会発表] Adipose tissue-derived stromal cells of steatohepatitis mice are useful for treatment of fibrosis-progressive NASH2020

    • 著者名/発表者名
      Akihiro Seki, Yoshio Sakai, Alessandro Nasti, Masatoshi Yamato, Kosuke Ishida, Hiiro Inui, Tuyen Thuy Bich Ho, Kazunori Kawaguchi, Takashi Wada, Shuichi Kaneko
    • 学会等名
      AASLD, The Liver Meeting 2020
    • 国際学会
  • [学会発表] Investigator-initiated clinical trial of autologous adipose tissue-derived regenerative (stem) cells therapy for steatohepatitis-related cirrhosis.2020

    • 著者名/発表者名
      Yoshio Sakai, Shinya Fukunishi, Masayuki Takamura, Oto Inoue, Soichiro Usui, Shinichiro Takashima, Kazunori Kawaguchi, Akihiro Seki, Akira Asai, Yusuke Tsuchimoto, Alessandro Nasti, Tuyen Thuy Bich Ho, Kazuhide Higuchi, Shuichi Kaneko
    • 学会等名
      AASLD, The Liver Meeting 2020
    • 国際学会
  • [学会発表] Adipose tissue derived stromal/stem cells suppress the hepatocyte apoptosis by restoring the Atf6 pathway activity in NASH mice.2020

    • 著者名/発表者名
      Masatoshi Yamato, Yoshio Sakai, Hiiro Inui, Akihiro Seki, Alessandro Nasti, Kosuke Ishida, Tuyen Thuy Bich Ho, Kazunori Kawaguchi, Takashi Wada, Shuichi Kaneko
    • 学会等名
      AASLD, The Liver Meeting 2020
    • 国際学会

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公開日: 2023-12-25  

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