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2021 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, 医薬保健学総合研究科, 特任准教授 (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 – 2023-03-31
キーワードNASH / uncultured ADSCs / ADSC
研究実績の概要

Freshly isolated uncultured adipose tissue-derived stromal cells (u-ADSCs) are useful for regenerative therapy. However, the detailed characteristics and therapeutic efficacy of u-ADSCs obtained from disease-affected hosts are unknown. We compared the properties and therapeutic efficacy of u-ADSCs obtained from wild-type mice and from a mouse model of non-alcoholic steatohepatitis (NASH). Wild-type u-ADSCs and NASH-derived u-ADSCs did not show marked differences as well as their therapeutic effects on NASH-related cirrhosis resulted highly similar, including reductions in inflammation and fibrosis. NASH-derived u-ADSCs, similar to wild-type u-ADSCs, are applicable for reparative and regenerative therapy in mice with NASH.

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

In FY2021, non-alcoholic steatohepatitis (NASH) model was established by feeding C57BL/6J mice an atherogenic high-fat diet for 4 (NASH(4w)) or 12 weeks (NASH(12w)), followed by the isolation and characterization of freshly isolated uncultured adipose tissue-derived stromal cells (u-ADSCs). Wild-type u-ADSCs or NASH-derived u-ADSCs were administered to mice with NASH cirrhosis, followed by assessment analyses. Therapeutic effects of NASH(4w)u-ADSCs and NASH(12w)u-ADSCs on mice with NASH-related cirrhosis were similar to the effect of wild-type u-ADSCs. Infiltration of inflammatory cells was reduced, the NAFLD Activity Score (NAS) and fibrosis improved, suggesting that the general properties of u-ADSCs were not significantly affected by NASH.

今後の研究の推進方策

The u-ADSCs are not solely dependent on MSCs for reparative/regenerative properties, but also other cells contribute to the therapeutic effect on hepatitis. The detailed characterization of u-ADSCs would be intriguing and it can provide insight into the mechanisms underlying specific functions of freshly isolated stromal cells of adipose tissue, particularly in regards of their reparative/restorative effects on injured organs. So, we are planning to further study the u-ADSCs and their derivatives for repair and regenerative therapy, such studies are expected to provide important information regarding specific enriched subpopulations for the development of enhanced cell therapies.

次年度使用額が生じた理由

Part of the funds were not used in FY2021 due to Coronavirus pandemic (ie.: funds for travelling to conferences not used, etc.). The rest of the expenses were processed as planned. For FY2022, it is expected to use the funds as planned.

  • 研究成果

    (4件)

すべて 2021

すべて 雑誌論文 (2件) (うち国際共著 2件、 査読あり 2件、 オープンアクセス 2件) 学会発表 (2件) (うち国際学会 2件)

  • [雑誌論文] Characterization of adipose tissue-derived stromal cells of mice with nonalcoholic fatty liver disease and their use for liver repair2021

    • 著者名/発表者名
      Masaaki Y*、Nasti A*、Seki A、Ishida K、Yamato M、Inui H、Ogawa N、Inagaki S、Ho TTB、Kawaguchi K、Yamashita T、Arai K、Yamashita T、Mizukoshi E、Inoue O、Takashima S、Usui S、Takamura M、Honda M、Wada T、Kaneko S、Sakai Y
    • 雑誌名

      Regenerative Therapy

      巻: 18 ページ: 497~507

    • DOI

      10.1016/j.reth.2021.11.005

    • 査読あり / オープンアクセス / 国際共著
  • [雑誌論文] Restorative effect of adipose tissue-derived stem cells on impaired hepatocytes through Notch signaling in non-alcoholic steatohepatitis mice2021

    • 著者名/発表者名
      Ishida Kosuke*、Seki Akihiro*、Kawaguchi Kazunori、Nasti Alessandro、Yamato Masatoshi、Inui Hiiro、Komura Takuya、Yamashita Taro、Arai Kuniaki、Yamashita Tatsuya、Mizukoshi Eishiro、Honda Masao、Wada Takashi、Harada Kenichi、Kaneko Shuichi、Sakai Yoshio
    • 雑誌名

      Stem Cell Research

      巻: 54 ページ: 102425~102425

    • DOI

      10.1016/j.scr.2021.102425

    • 査読あり / オープンアクセス / 国際共著
  • [学会発表] Jagged1 ON ADIPOSE TISSUE-DERIVED STROMAL / STEM CELLS IS INVOLVED IN THE RESTORATIVE EFFECT ON MURINE NON-ALCOHOLIC STEATOHEPATITIS.2021

    • 著者名/発表者名
      Kosuke Ishida, Yoshio Sakai, Akihiro Seki, Kazunori Kawaguchi, Alessandro Nasti, Takashi Wada and Shuichi Kaneko
    • 学会等名
      AASLD, The Liver Meeting 2021
    • 国際学会
  • [学会発表] Restorative effect of adipose tissue-derived mesenchymal stem cells towards impaired hepatocytes via Notch signaling in a murine model of non-alcoholic steatohepatitis mice2021

    • 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
      The 44th Annual Meeting of the Molecular Biology Society of Japan
    • 国際学会

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公開日: 2022-12-28  

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