Obeticholic acid-loaded exosomes attenuate liver fibrosis through dual targeting of the FXR signaling pathway and ECM remodeling
Open accessAbstract
End-stage of liver fibrosis as a precancerous state could lead to cirrhosis and hepatocellular carcinoma which liver transplantation is the only effective treatment. Previous studies have indicated that farnesoid X receptor (FXR) agonists, such as obeticholic acid (OCA) protect against hepatic injuries. However, free OCA administration results in side effects in clinical trials that could be alleviated by applying bio carriers such as MSC-derived exosomes (Exo) with the potential to mimic the biological regenerative effect of their parent cells, as proposed in this study. Loading OCA into the Exo was conducted via water bath sonication. Ex vivo bio distribution studies validated the Exo-loaded OCA more permanently accumulated in the liver. Using CCL4-induced liver fibrosis, we proposed whether Exo isolated from human Warton's Jelly mesenchymal stem cells loaded with a minimal dosage of OCA can facilitate liver recovery. Notably, Exo-loaded OCA exerted additive anti-fibrotic efficacy on histopathological features in CCL4-induced fibrotic mice. Compared to baseline, Exo-mediated delivery OCA results in marked improvements in the fibrotic-related indicators as well as serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) concentrations. Accordingly, the synergistic impact of Exo-loaded OCA as a promising approach is associated with the inactivation of hepatic stellate cells (HSCs), extracellular matrix (ECM) remodeling, and Fxr-Cyp7a1 cascade on CCL4-induced liver fibrosis mice. In conclusion, our data confirmed the additive protective effects of Exo-loaded OCA in fibrotic mice, which suggests a valuable therapeutic strategy to combat liver fibrosis. Furthermore, the use of Exo for accurate drug delivery to the liver tissue can be inspiring.
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MSC-Exos loaded with obeticholic acid or luteolin exhibited superior anti-fibrotic effects compared with either drugs or MSC-Exos alone.
“It has been reported that MSC-Exos loaded with obeticholic acid or luteolin exhibited superior anti-fibrotic effects compared with either drugs or MSC-Exos alone [266, 267].”
From Mechanisms, efficacy, and future perspectives of cellular-based therapies for liver fibrosis/cirrhosis: focusing on mesenchymal stromal cells (2025) · cites this paper as [266]
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Self-citationExtracellular vesicles: emerging therapeutic agents for liver fibrosis
Chiabotto, G., Semnani, A., Ceccotti, E., & Bruno, S. (2025) · Extracellular Vesicles and Circulating Nucleic Acids · doi:10.20517/evcna.2025.08 · Cited by 13 · see citing works
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“It has been reported that MSC-Exos loaded with obeticholic acid or luteolin exhibited superior anti-fibrotic effects compared with either drugs or MSC-Exos alone [266, 267].”
- Authors
- Azizsoltani, A., Hatami, B., Zali, M. R., Mahdavi, V., Baghaei, K., & Alizadeh, E.
- Affiliations
- Tabriz University of Medical Sciences (IR)
- Research Institute for Gastroenterology and Liver Diseases (IR)
- Agricultural Research & Education Organization (IR)
- Corresponding author
- Baghaei, Kaveh
- Alizadeh, Effat
- ORCID
- Venue
- Biomedicine & Pharmacotherapy
- Publisher
- Elsevier BV
- Published
- 2023-12
- Volume
- 168
- Pages
- 115777
- ISSN
- 0753-3322 (ISSN-L)
- OpenAlex
- W4388066669
- Cited by
- 40
- References
- 7
- Citations by year
- 2026: 9 · 2025: 16 · 2024: 15
- FWCI
- 3.56
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Biomedicine & Pharmacotherapy (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Tabriz University of Medical Sciences (65016)
- Shaheed Beheshti University of Medical Sciences Research Institute for Gastroenterology and Liver Diseases (1148)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Keywords
- obeticholic acid, exosomes, liver fibrosis, farnesoid X receptor, hepatic stellate cells, extracellular matrix remodeling, CYP7A1, drug delivery, carbon tetrachloride-induced liver injury, hepatoprotection
- MeSH terms
- Animals, Chenodeoxycholic Acid, Extracellular Matrix, Fibrosis, Humans, Liver, Liver Cirrhosis, Signal Transduction, Mice, Exosomes
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