Characterization of adipose tissue-derived stromal cells of mice with nonalcoholic fatty liver disease and their use for liver repair

• Published in: Regenerative therapy 2021-12, Vol.18, p.497-507
• Main Authors: Yano, Masaaki, Nasti, Alessandro, Seki, Akihiro, Ishida, Kosuke, Yamato, Masatoshi, Inui, Hiiro, Ogawa, Norihiko, Inagaki, Shingo, Ho, Tuyen Thuy Bich, Kawaguchi, Kazunori, Yamashita, Taro, Arai, Kuniaki, Yamashita, Tatsuya, Mizukoshi, Eishiro, Inoue, Oto, Takashima, Shinichiro, Usui, Soichiro, Takamura, Masayuki, Honda, Masao, Wada, Takashi, Kaneko, Shuichi, Sakai, Yoshio
• Format: Article
• Language: English
• Subjects: Adipose tissue; Mesenchymal stem cells; Non-alcoholic fatty liver disease; Original; Stromal cells
• ISSN: 2352-3204; 2352-3204
• DOI: 10.1016/j.reth.2021.11.005

Freshly isolated uncultured adipose tissue-derived stromal cells (u-ADSCs), containing miscellaneous cells like the relatively abundant mesenchymal stem cells, are attractive for repair and regenerative therapy. However, the detailed characteristics and therapeutic efficacy of u-ADSCs obtained from disease-affected hosts are unknown. We compared the properties of u-ADSCs obtained from wild-type mice and from a mouse model of non-alcoholic steatohepatitis (NASH). The 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 u-ADSCs. Wild-type u-ADSCs or NASH-derived u-ADSCs were administered to mice with NASH cirrhosis, followed by analyses of hepatic inflammatory cells, antigen profiles, fibrosis, and gene expression. Wild-type u-ADSCs and NASH-derived u-ADSCs did not show marked differences in surface antigen profiles. In NASH (4w) u-ADSCs, but not NASH (12w) u-ADSCs, the frequencies of the leukocyte markers CD11b, CD45, and CD44 were elevated; furthermore, we observed an increase in the M1/M2 macrophage ratio only in NASH (12w) u-ADSCs. Only in NASH-4w u-ADSCs, the expression levels cell cycle-related genes were higher than those in u-ADSCs. Wild-type u-ADSCs administered to mice with NASH-related cirrhosis decreased the infiltration of CD11b+, F4/80+, and Gr-1+ inflammatory cells, ameliorated fibrosis, and had a restorative effect on liver tissues, as determined by gene expression profiles and the NAFLD activity score. The therapeutic effects of NASH (4w) u-ADSCs and NASH (12w) u-ADSCs on NASH-related cirrhosis were highly similar to the effect of wild-type u-ADSCs, 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. •Uncultured adipose tissue-derived stromal cells (u-ADSCs) in regenerative therapy.•Nonalcoholic steatohepatitis (NASH) mice model was established.•We confirmed the efficacy of u-ADSCs for treatment of cirrhotic mice.•We studied the NASH mouse model-derived u-ADSCs for treatment of cirrhotic mice.•NASH-u-ADSCs and wild-type u-ADSCs are anti-inflammatory and effective for cirrhosis.