BMP7-Loaded Human Umbilical Cord Mesenchymal Stem Cell-Derived Small Extracellular Vesicles Ameliorate Liver Fibrosis by Targeting Activated Hepatic Stellate Cells
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Purpose: Human umbilical cord mesenchymal stem cell (hucMSC)-derived small extracellular vesicles (sEVs) are natural nanocarriers with promising potential in treating liver fibrosis and have widespread applications in the fields of nanomedicine and regenerative medicine. However, the therapeutic efficacy of natural hucMSC-sEVs is currently limited owing to their non-specific distribution in vivo and partial removal by mononuclear macrophages following systemic delivery. Thus, the therapeutic efficacy can be improved through the development of engineered hucMSC-sEVs capable to overcome these limitations. Patients and Methods: ) in parental cells. This was achieved using lentiviral transfection, following which BMP7-loaded hucMSC-sEVs were isolated through ultracentrifugation. First, the liver fibrosis was induced in C57BL/6J mice by intraperitoneal injection of 50% carbon tetrachloride (CCL4) twice a week for 8 weeks. These mice were subsequently treated with BMP7+sEVs via tail vein injection, and the anti-liver fibrosis effect of BMP7+sEVs was validated using small animal in vivo imaging, immunohistochemistry (IHC), tissue immunofluorescence, and enzyme-linked immunosorbent assay (ELISA). Finally, cell function studies were performed to confirm the in vivo results. Results: Liver imaging and liver histopathology confirmed that the engineered hucMSC-sEVs could reach the liver of mice and aggregate around activated hepatic stellate cells (aHSCs) with a significantly stronger anti-liver fibrosis effect of BMP7-loaded hucMSC-sEVs compared to those of blank or negative control-transfected hucMSC-sEVs. In vitro, BMP7-loaded hucMSC-sEVs promoted the phenotypic reversal of aHSCs and inhibited their proliferation to enhance the anti-fibrotic effects. Conclusion: These engineered BMP7-loaded hucMSC-sEVs offer a novel and promising strategy for the clinical treatment of liver fibrosis.
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BMP7-loaded MSC-EVs inhibited HSC proliferation to enhance anti-fibrotic effects.
“Zhu et al. reported that BMP7-loaded MSC-EVs inhibited HSC proliferation to enhance the anti-fibrotic effects [249].”
From Mechanisms, efficacy, and future perspectives of cellular-based therapies for liver fibrosis/cirrhosis: focusing on mesenchymal stromal cells (2025) · cites this paper as [249]
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- Authors
- Zhu, D., Sun, Z., Wei, J., Zhang, Y., An, W., Lin, Y., & Li, X.
- Affiliations
- Lanzhou University (CN)
- First Hospital of Lanzhou University (CN)
- Corresponding author
- Li, Xun
- Venue
- International Journal of Nanomedicine
- Publisher
- Informa UK Limited
- Published
- 2024-04
- Volume
- Volume 19
- Pages
- 3475-3495
- ISSN
- 1176-9114 (ISSN-L)
- 1178-2013
- PMC
- PMC11018131
- OpenAlex
- W4394721855
- Cited by
- 17
- References
- 53
- Citations by year
- 2026: 7 · 2025: 7 · 2024: 3
- FWCI
- 2.31
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- International Journal of Nanomedicine (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Dove Medical Press (Taylor and Francis Group) (submittedVersion, cc-by-nc)
- Funders
- National Natural Science Foundation of China (32171610, 82060119)
- Natural Science Foundation of Gansu Province (21JR1RA072, 82060119)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- liver fibrosis, small extracellular vesicles, human umbilical cord mesenchymal stem cells, BMP-7, hepatic stellate cells, engineered extracellular vesicles, carbon tetrachloride-induced fibrosis, antifibrotic therapy, vesicle targeting, stem cell-derived vesicles
- MeSH terms
- Extracellular Vesicles, Animals, Fibrosis, Humans, Liver Cirrhosis, Mice, Inbred C57BL, Umbilical Cord, Mice, Hepatic Stellate Cells, Bone Morphogenetic Protein 7, Mesenchymal Stem Cells
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