Characterization of adipose tissue-derived stromal cells of mice with nonalcoholic fatty liver disease and their use for liver repair.
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
Journal
Regenerative therapy
ISSN: 2352-3204
Titre abrégé: Regen Ther
Pays: Netherlands
ID NLM: 101709085
Informations de publication
Date de publication:
Dec 2021
Dec 2021
Historique:
received:
03
08
2021
revised:
01
11
2021
accepted:
18
11
2021
entrez:
20
12
2021
pubmed:
21
12
2021
medline:
21
12
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 34926735
doi: 10.1016/j.reth.2021.11.005
pii: S2352-3204(21)00087-0
pmc: PMC8649123
doi:
Types de publication
Journal Article
Langues
eng
Pagination
497-507Informations de copyright
© 2021 The Japanese Society for Regenerative Medicine. Production and hosting by Elsevier B.V.
Déclaration de conflit d'intérêts
None declared.
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