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Comparative Evaluation of Anti-Fibrotic Effect of Tissue Specific Mesenchymal Stem Cells Derived Extracellular Vesicles for the Amelioration of CCl4 Induced Chronic Liver Injury
Abstract
Mesenchymal Stem Cells (MSCs) derived Extracellular Vesicles (EVs) have emerged as an effective candidate for amelioration of liver fibrosis. However, the effect and the mechanisms of MSC-EVs in liver repair remains elusive. In this study, we have evaluated the differential regenerative efficacy of EVs derived from two different human tissue-specific MSCs (Adipose tissue; AD-MSC and Wharton's Jelly; WJ-MSC), in a murine model of chronic liver fibrosis. Mouse model of chronic liver injury was induced by carbon tetrachloride (CCl 4) injection, followed by administration of EVs via the tail vein. Both quantitative and qualitative assessment was done to evaluate the hepatic regenerative potential of tissue specific MSC-extracellular vesicles. EVs, regardless of their MSC source, were found to be effective in alleviating chronic liver fibrosis, as demonstrated by macroscopic alterations in the liver. According to the findings of the comprehensive study, there were subtle variations in the tissue specific MSCs-EVs mediated approaches. A greater anti-fibrotic impact was demonstrated by AD-MSC derived EVs through extracellular matrix alteration and hepatocyte proliferation. WJ-MSC EVs, on the other hand, have an anti-inflammatory effect, as evidenced by alterations in the expression of pro- and anti-inflammatory cytokines. Furthermore, cargo profiling of these EVs revealed differences in the miRNA and protein expression, as well as the pathways that they were associated. Comparative overview of regression of fibrosis using tissue specific MSC derived EVs (credits BioRender.com ).
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“In CCl4-injured mouse models, MSC-derived EVs promoted liver regeneration, as evidenced by elevated hepatocyte proliferation marker PCNA [200].”
From Mechanisms, efficacy, and future perspectives of cellular-based therapies for liver fibrosis/cirrhosis: focusing on mesenchymal stromal cells (2025) · cites this paper as [200]
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“Hydrogen peroxide (H2O2) induces oxidative stress by disrupting the cellular redox circuit and damaging DNA, thereby altering fundamental cellular functions such as proliferation and induce its apoptosis, a condition associated with progression of liver diseases [31].”
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Mesenchymal Stem Cell–Derived Exosomes in Various Chronic Liver Diseases: Hype or Hope?
Zhu, L., Wang, Q., Guo, M., Fang, H., Li, T., Zhu, Y., Jiang, H., Xiao, P., & Hu, M. (2024) · Journal of Inflammation Research · doi:10.2147/jir.s439974 · Cited by 21
Pan, X., Gao, T., & Wang, B. (2025) · Cell & Bioscience · doi:10.1186/s13578-025-01520-9 · Cited by 2
“In CCl4-injured mouse models, MSC-derived EVs promoted liver regeneration, as evidenced by elevated hepatocyte proliferation marker PCNA [200].”
Metadata
- Authors
- Gupta, S., Pinky, Vishal, Sharma, H., Soni, N., Rao, E. P., Dalela, M., Yadav, A., Nautiyal, N., Kumar, A., Nayak, B., Banerjee, A., Dinda, A. K., & Mohanty, S.
- Affiliations
- All India Institute of Medical Sciences (IN)
- Regional Centre for Biotechnology (IN)
- Institute of Liver and Biliary Sciences (IN)
- Corresponding author
- Mohanty, Sujata
- ORCID
- Venue
- Stem Cell Reviews and Reports
- Published
- 2021-12-02
- Volume
- 18
- Issue
- 3
- Pages
- 1097-1112
- ISSN
- 1550-8943 (ISSN-L)
- 2629-3269
- 2629-3277
- OpenAlex
- W3216878350
- Cited by
- 35
- References
- 2
- Citations by year
- 2026: 1 · 2025: 7 · 2024: 15 · 2023: 9 · 2022: 3
- FWCI
- 2.12
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Stem Cell Reviews and Reports (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Mesenchymal stem cell research
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- mesenchymal stem cell-derived extracellular vesicles, liver fibrosis, chronic liver injury, carbon tetrachloride, adipose-derived stem cells, Wharton's jelly mesenchymal stem cells, liver regeneration, extracellular matrix, hepatocyte proliferation, anti-inflammatory activity, cytokine expression, EV cargo
- MeSH terms
- Extracellular Vesicles, Animals, Anti-Inflammatory Agents, Fibrosis, Liver Cirrhosis, Mice, Mesenchymal Stem Cells
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- CoChat. (2026). Citation check: Comparative Evaluation of Anti-Fibrotic Effect of Tissue Specific Mesenchymal Stem Cells Derived Extracellular Vesicles for the Amelioration of CCl4 Induced Chronic Liver Injury. https://app.cochat.ai/papers/10.1007/s12015-021-10313-9
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- Gupta, S., Pinky, Vishal, Sharma, H., Soni, N., Rao, E. P., Dalela, M., Yadav, A., Nautiyal, N., Kumar, A., Nayak, B., Banerjee, A., Dinda, A. K., & Mohanty, S. (2022). Comparative Evaluation of Anti-Fibrotic Effect of Tissue Specific Mesenchymal Stem Cells Derived Extracellular Vesicles for the Amelioration of CCl4 Induced Chronic Liver Injury. Stem Cell Reviews and Reports. https://doi.org/10.1007/s12015-021-10313-9