Characterization of adipose tissue-derived stromal cells of mice with nonalcoholic fatty liver disease and their use for liver repair.
Regen Ther
; 18: 497-507, 2021 Dec.
Article
em En
| MEDLINE
| ID: mdl-34926735
ABSTRACT
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.
AST, aspartate aminotransferase; AT-HF, atherogenic high-fat; Adipose tissue; FCM, flow cytometry; HICs, hepatic inflammatory cells; LD, lactate dehydrogenase; MSCs, mesenchymal stem cells; Mesenchymal stem cells; NAFLD, nonalcoholic fatty liver disease; NAS, NAFLD activity score; NASH (12 w) u-ADSCs, NASH (12 weeks)-derived u-ADSCs; NASH (4w) u-ADSCs, NASH (4 weeks)-derived u-ADSCs; NASH, nonalcoholic steatohepatitis; Non-alcoholic fatty liver disease; Stromal cells; qRT-PCR, quantitative real-time polymerase chain reaction; u-ADSCs, uncultured adipose tissue-derived stromal cells
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Base de dados:
MEDLINE
Tipo de estudo:
Prognostic_studies
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article