Huc-MSCs-derived exosomes alleviate non-alcoholic steatohepatitis by regulating macrophages polarization through miR-24-3p/STING axis
Abstract Background There’s a scarcity of drugs effective against nonalcoholic steatohepatitis (NASH). Exosomes from Human umbilical cord mesenchymal stem cells (huc-MSCs) show potential in managing glycolipid metabolism and the immune response. Therefore, further investigations are required to expl...
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BMC
2025-02-01
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| Series: | Stem Cell Research & Therapy |
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| Online Access: | https://doi.org/10.1186/s13287-025-04197-6 |
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| author | Wei Jiang Qingmin Zeng Chang-Hai Liu Yonghong Wang Shisheng Wang Enqiang Chen Ming Wang Taoyou Zhou Lang Bai Dongbo Wu Hong Tang |
| author_facet | Wei Jiang Qingmin Zeng Chang-Hai Liu Yonghong Wang Shisheng Wang Enqiang Chen Ming Wang Taoyou Zhou Lang Bai Dongbo Wu Hong Tang |
| author_sort | Wei Jiang |
| collection | DOAJ |
| description | Abstract Background There’s a scarcity of drugs effective against nonalcoholic steatohepatitis (NASH). Exosomes from Human umbilical cord mesenchymal stem cells (huc-MSCs) show potential in managing glycolipid metabolism and the immune response. Therefore, further investigations are required to explore their application in NASH and the underlying mechanisms. Methods C57BL/6J mice were fed with a western diet for 12 weeks to induce NASH, and huc-MSCs exosomes (MSCs-exo) were administered during the feeding period. The effect of MSCs-exo was evaluated by monitoring changes in body weight, fat distribution, blood glucose, and insulin levels, and analyzing pathological alterations in liver tissue. Mechanism investigations were carried out using flow cytometry, immunofluorescence staining, and other experimental techniques. Results MSCs-exo could reduce liver fat, inflammation, fibrosis, and improved metabolism to alleviate the progression of NASH. Besides, MSCs-exo could decrease macrophage accumulation in the liver, encouraging M2 over M1 macrophage polarization. Furthermore, our study found that MSCs-exo had a high expression of miR-24-3p, which may regulate macrophage polarization by targeting the interferon-stimulated genes (STING) gene in macrophages, with its overexpression amplifying MSCs-exo’s NASH benefits. Conclusions These findings suggest that the therapeutic effect of MSCs-exo on NASH may be attributed to the regulation of macrophage M2 polarization through miR-24-3p targeting STING. This provides a scientific basis for future clinical application. |
| format | Article |
| id | doaj-art-0b3eb5ab08604c92bb3046e7636d2de8 |
| institution | OA Journals |
| issn | 1757-6512 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMC |
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| series | Stem Cell Research & Therapy |
| spelling | doaj-art-0b3eb5ab08604c92bb3046e7636d2de82025-08-20T02:15:15ZengBMCStem Cell Research & Therapy1757-65122025-02-0116111410.1186/s13287-025-04197-6Huc-MSCs-derived exosomes alleviate non-alcoholic steatohepatitis by regulating macrophages polarization through miR-24-3p/STING axisWei Jiang0Qingmin Zeng1Chang-Hai Liu2Yonghong Wang3Shisheng Wang4Enqiang Chen5Ming Wang6Taoyou Zhou7Lang Bai8Dongbo Wu9Hong Tang10Center of Infectious Diseases, West China Hospital, Sichuan UniversityCenter of Infectious Diseases, West China Hospital, Sichuan UniversityCenter of Infectious Diseases, West China Hospital, Sichuan UniversityCenter of Infectious Diseases, West China Hospital, Sichuan UniversityLiver Surgery and Liver Transplant Center, Department of Clinical Research Management, West China Hospital, Sichuan UniversityCenter of Infectious Diseases, West China Hospital, Sichuan UniversityCenter of Infectious Diseases, West China Hospital, Sichuan UniversityCenter of Infectious Diseases, West China Hospital, Sichuan UniversityCenter of Infectious Diseases, West China Hospital, Sichuan UniversityCenter of Infectious Diseases, West China Hospital, Sichuan UniversityCenter of Infectious Diseases, West China Hospital, Sichuan UniversityAbstract Background There’s a scarcity of drugs effective against nonalcoholic steatohepatitis (NASH). Exosomes from Human umbilical cord mesenchymal stem cells (huc-MSCs) show potential in managing glycolipid metabolism and the immune response. Therefore, further investigations are required to explore their application in NASH and the underlying mechanisms. Methods C57BL/6J mice were fed with a western diet for 12 weeks to induce NASH, and huc-MSCs exosomes (MSCs-exo) were administered during the feeding period. The effect of MSCs-exo was evaluated by monitoring changes in body weight, fat distribution, blood glucose, and insulin levels, and analyzing pathological alterations in liver tissue. Mechanism investigations were carried out using flow cytometry, immunofluorescence staining, and other experimental techniques. Results MSCs-exo could reduce liver fat, inflammation, fibrosis, and improved metabolism to alleviate the progression of NASH. Besides, MSCs-exo could decrease macrophage accumulation in the liver, encouraging M2 over M1 macrophage polarization. Furthermore, our study found that MSCs-exo had a high expression of miR-24-3p, which may regulate macrophage polarization by targeting the interferon-stimulated genes (STING) gene in macrophages, with its overexpression amplifying MSCs-exo’s NASH benefits. Conclusions These findings suggest that the therapeutic effect of MSCs-exo on NASH may be attributed to the regulation of macrophage M2 polarization through miR-24-3p targeting STING. This provides a scientific basis for future clinical application.https://doi.org/10.1186/s13287-025-04197-6Nonalcoholic steatohepatitisMesenchymal stem cellsExosomesMacrophagesSTINGmiR-24-3p |
| spellingShingle | Wei Jiang Qingmin Zeng Chang-Hai Liu Yonghong Wang Shisheng Wang Enqiang Chen Ming Wang Taoyou Zhou Lang Bai Dongbo Wu Hong Tang Huc-MSCs-derived exosomes alleviate non-alcoholic steatohepatitis by regulating macrophages polarization through miR-24-3p/STING axis Stem Cell Research & Therapy Nonalcoholic steatohepatitis Mesenchymal stem cells Exosomes Macrophages STING miR-24-3p |
| title | Huc-MSCs-derived exosomes alleviate non-alcoholic steatohepatitis by regulating macrophages polarization through miR-24-3p/STING axis |
| title_full | Huc-MSCs-derived exosomes alleviate non-alcoholic steatohepatitis by regulating macrophages polarization through miR-24-3p/STING axis |
| title_fullStr | Huc-MSCs-derived exosomes alleviate non-alcoholic steatohepatitis by regulating macrophages polarization through miR-24-3p/STING axis |
| title_full_unstemmed | Huc-MSCs-derived exosomes alleviate non-alcoholic steatohepatitis by regulating macrophages polarization through miR-24-3p/STING axis |
| title_short | Huc-MSCs-derived exosomes alleviate non-alcoholic steatohepatitis by regulating macrophages polarization through miR-24-3p/STING axis |
| title_sort | huc mscs derived exosomes alleviate non alcoholic steatohepatitis by regulating macrophages polarization through mir 24 3p sting axis |
| topic | Nonalcoholic steatohepatitis Mesenchymal stem cells Exosomes Macrophages STING miR-24-3p |
| url | https://doi.org/10.1186/s13287-025-04197-6 |
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