Adipose-derived mesenchymal stem cell-secreted extracellular vesicles alleviate non-alcoholic fatty liver disease via delivering miR-223-3p
Open accessAbstract
Increasing studies have identified the potential of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) in non-alcoholic fatty liver disease (NAFLD) treatment. Hence, we further focused on the potential of adipose-derived MSC (ADSC)-EVs in NAFLD by delivering miR-223-3p. The uptake of isolated ADSC-EVs by hepatocytes was assessed, and the expression of miR-223-3p in ADSC-EVs and hepatocytes was characterized. It was established that miR-223-3p, enriched in ADSC-EVs, could be delivered by ADSC-EVs into hepatocytes. Using co-culture system and gain-of-function approach, we evaluated the effect of ADSC-EVs carrying miR-223-3p on lipid accumulation and liver fibrosis in pyrrolizidine alkaloids (PA)-induced hepatocytes and a high-fat diet-induced NAFLD mouse model. Bioinformatics websites and dual-luciferase reporter gene assay were performed to determine the interactions between miR-223-3p and E2F1, which was further validated by rescue experiments. ADSC-EVs containing miR-223-3p displayed suppressive effects on lipid accumulation and liver fibrosis through E2F1 inhibition, since E2F1 was demonstrated as a target gene of miR-223-3p. The protective role of ADSC-EVs by delivering miR-223-3p was then confirmed in the mouse model. Collectively, this study elucidated that ADSC-EVs delayed the progression NAFLD through the delivery of anti-fibrotic miR-223-3p and subsequent E2F1 suppression, which may suggest miR-223-3p-loaded ADSC-EVs to be a potential therapeutic approach for NAFLD.
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In a NAFLD model, AD-MSC-EV-derived miR-223-3p reduces lipid accumulation through E2F1 inhibition.
“In a NAFLD model, AD-MSC-EV-derived miR-223-3p has been reported to reduce lipid accumulation through E2F1 inhibition [207].”
From Mechanisms, efficacy, and future perspectives of cellular-based therapies for liver fibrosis/cirrhosis: focusing on mesenchymal stromal cells (2025) · cites this paper as [207]
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Mechanisms and disease consequences of nonalcoholic fatty liver disease
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Pan, X., Gao, T., & Wang, B. (2025) · Cell & Bioscience · doi:10.1186/s13578-025-01520-9 · Cited by 2 · see citing works
“In a NAFLD model, AD-MSC-EV-derived miR-223-3p has been reported to reduce lipid accumulation through E2F1 inhibition [207].”
- Authors
- Niu, Q., Wang, T., Wang, Z., Wang, F., Huang, D., Sun, H., & Liu, H.
- Affiliations
- Affiliated Hospital of Qingdao University (CN)
- Corresponding author
- Liu, Hanyun
- Venue
- Adipocyte
- Publisher
- Informa UK Limited
- Published
- 2022-09-12
- Volume
- 11
- Issue
- 1
- Pages
- 572-587
- ISSN
- 2162-3945 (ISSN-L)
- 2162-397X
- PMC
- PMC9481107
- OpenAlex
- W4295259903
- Cited by
- 70
- References
- 2
- Citations by year
- 2026: 16 · 2025: 22 · 2024: 19 · 2023: 11 · 2022: 2
- FWCI
- 4.41
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Adipocyte (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- there is no funding associated
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Keywords
- adipose-derived stem cells, extracellular vesicles, non-alcoholic fatty liver disease, miR-223-3p, E2F1, liver fibrosis, hepatic lipid accumulation, pyrrolizidine alkaloids, high-fat diet, cell-free therapy, microRNA delivery
- MeSH terms
- Extracellular Vesicles, Animals, Lipids, Liver Cirrhosis, MicroRNAs, Mice, Mesenchymal Stem Cells, Non-alcoholic Fatty Liver Disease
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