| Autor: |
Masaaki Yano, Alessandro Nasti, Akihiro Seki, Kosuke Ishida, Masatoshi Yamato, Hiiro Inui, Norihiko Ogawa, Shingo Inagaki, Tuyen Thuy Bich Ho, Kazunori Kawaguchi, Taro Yamashita, Kuniaki Arai, Tatsuya Yamashita, Eishiro Mizukoshi, Oto Inoue, Shinichiro Takashima, Soichiro Usui, Masayuki Takamura, Masao Honda, Takashi Wada, Shuichi Kaneko, Yoshio Sakai |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Předmět: |
|
| Zdroj: |
Regenerative Therapy, Vol 18, Iss , Pp 497-507 (2021) |
| Druh dokumentu: |
article |
| ISSN: |
2352-3204 |
| DOI: |
10.1016/j.reth.2021.11.005 |
| Popis: |
Introduction: 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). Methods: 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. Results: 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. Conclusions: NASH-derived u-ADSCs, similar to wild-type u-ADSCs, are applicable for reparative and regenerative therapy in mice with NASH. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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