Mesenchymal stromal cell-derived extracellular vesicles as nanotherapeutics for concanavalin a-induced hepatitis: modulating the gut‒liver axis
Abstract Background As cell-free nanotherapeutics, extracellular vesicles derived from mesenchymal stem cells (MSC-EVs) have shown potential therapeutic action against liver diseases. However, their effects on autoimmune hepatitis (AIH) are not yet well understood. Methods and results In this study,...
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BMC
2025-01-01
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| Series: | Stem Cell Research & Therapy |
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| Online Access: | https://doi.org/10.1186/s13287-024-04013-7 |
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| author | Fan Yang Beibei Ni Xiaoqi Liang Yizhan He Chao Yuan Jiajie Chu Yiju Huang Hongyu Zhong Li Yang Jianxi Lu Yan Xu Qi Zhang Wenjie Chen |
| author_facet | Fan Yang Beibei Ni Xiaoqi Liang Yizhan He Chao Yuan Jiajie Chu Yiju Huang Hongyu Zhong Li Yang Jianxi Lu Yan Xu Qi Zhang Wenjie Chen |
| author_sort | Fan Yang |
| collection | DOAJ |
| description | Abstract Background As cell-free nanotherapeutics, extracellular vesicles derived from mesenchymal stem cells (MSC-EVs) have shown potential therapeutic action against liver diseases. However, their effects on autoimmune hepatitis (AIH) are not yet well understood. Methods and results In this study, we utilized a well-established concanavalin A (Con A)-induced fulminant hepatitis mouse model to investigate the effects of MSC-EVs on AIH. We found that MSC-EVs provide significant protection against Con A-induced hepatitis in C57BL/6 male mice, with their effectiveness being critically dependent on the gut microbiota. MSC-EVs modulate the composition of the gut microbiota, particularly by increasing the abundance of norank_f__Muribaculaceae, and impact liver metabolic profiles, leading to significant amelioration of liver injury. The identification of Acetyl-DL-Valine as a protective metabolite underscores the therapeutic potential of targeting gut‒liver axis interactions in liver diseases. Conclusion Overall, our data demonstrate that MSC-EVs exhibit nanotherapeutic potential in Con A-induced hepatitis and provide new insights into the treatment of autoimmune hepatitis. Graphical Abstract |
| format | Article |
| id | doaj-art-dd19e8820ef544129ca01c10ecdb24a6 |
| institution | Kabale University |
| issn | 1757-6512 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj-art-dd19e8820ef544129ca01c10ecdb24a62025-01-12T12:10:18ZengBMCStem Cell Research & Therapy1757-65122025-01-0116111610.1186/s13287-024-04013-7Mesenchymal stromal cell-derived extracellular vesicles as nanotherapeutics for concanavalin a-induced hepatitis: modulating the gut‒liver axisFan Yang0Beibei Ni1Xiaoqi Liang2Yizhan He3Chao Yuan4Jiajie Chu5Yiju Huang6Hongyu Zhong7Li Yang8Jianxi Lu9Yan Xu10Qi Zhang11Wenjie Chen12Biotherapy Centre, The Third Affiliated Hospital, Sun Yat-Sen UniversityCell–Gene Therapy Translational Medicine Research Centre, The Third Affiliated Hospital, Sun Yat-Sen UniversityCell–Gene Therapy Translational Medicine Research Centre, The Third Affiliated Hospital, Sun Yat-Sen UniversityDepartment of Neurology, The Third Affiliated Hospital of Sun Yat-Sen University Zhaoqing hospitalGeneral practice, Guangdong provincial people’s hospitalCell–Gene Therapy Translational Medicine Research Centre, The Third Affiliated Hospital, Sun Yat-Sen UniversityCell–Gene Therapy Translational Medicine Research Centre, The Third Affiliated Hospital, Sun Yat-Sen UniversityCell–Gene Therapy Translational Medicine Research Centre, The Third Affiliated Hospital, Sun Yat-Sen UniversityBiotherapy Centre, The Third Affiliated Hospital, Sun Yat-Sen UniversityBiotherapy Centre, The Third Affiliated Hospital, Sun Yat-Sen UniversityBiotherapy Centre, The Third Affiliated Hospital, Sun Yat-Sen UniversityBiotherapy Centre, The Third Affiliated Hospital, Sun Yat-Sen UniversityBiotherapy Centre, The Third Affiliated Hospital, Sun Yat-Sen UniversityAbstract Background As cell-free nanotherapeutics, extracellular vesicles derived from mesenchymal stem cells (MSC-EVs) have shown potential therapeutic action against liver diseases. However, their effects on autoimmune hepatitis (AIH) are not yet well understood. Methods and results In this study, we utilized a well-established concanavalin A (Con A)-induced fulminant hepatitis mouse model to investigate the effects of MSC-EVs on AIH. We found that MSC-EVs provide significant protection against Con A-induced hepatitis in C57BL/6 male mice, with their effectiveness being critically dependent on the gut microbiota. MSC-EVs modulate the composition of the gut microbiota, particularly by increasing the abundance of norank_f__Muribaculaceae, and impact liver metabolic profiles, leading to significant amelioration of liver injury. The identification of Acetyl-DL-Valine as a protective metabolite underscores the therapeutic potential of targeting gut‒liver axis interactions in liver diseases. Conclusion Overall, our data demonstrate that MSC-EVs exhibit nanotherapeutic potential in Con A-induced hepatitis and provide new insights into the treatment of autoimmune hepatitis. Graphical Abstracthttps://doi.org/10.1186/s13287-024-04013-7Extracellular vesiclesMesenchymal stromal cellsCon A-induced hepatitisGut microbiota |
| spellingShingle | Fan Yang Beibei Ni Xiaoqi Liang Yizhan He Chao Yuan Jiajie Chu Yiju Huang Hongyu Zhong Li Yang Jianxi Lu Yan Xu Qi Zhang Wenjie Chen Mesenchymal stromal cell-derived extracellular vesicles as nanotherapeutics for concanavalin a-induced hepatitis: modulating the gut‒liver axis Stem Cell Research & Therapy Extracellular vesicles Mesenchymal stromal cells Con A-induced hepatitis Gut microbiota |
| title | Mesenchymal stromal cell-derived extracellular vesicles as nanotherapeutics for concanavalin a-induced hepatitis: modulating the gut‒liver axis |
| title_full | Mesenchymal stromal cell-derived extracellular vesicles as nanotherapeutics for concanavalin a-induced hepatitis: modulating the gut‒liver axis |
| title_fullStr | Mesenchymal stromal cell-derived extracellular vesicles as nanotherapeutics for concanavalin a-induced hepatitis: modulating the gut‒liver axis |
| title_full_unstemmed | Mesenchymal stromal cell-derived extracellular vesicles as nanotherapeutics for concanavalin a-induced hepatitis: modulating the gut‒liver axis |
| title_short | Mesenchymal stromal cell-derived extracellular vesicles as nanotherapeutics for concanavalin a-induced hepatitis: modulating the gut‒liver axis |
| title_sort | mesenchymal stromal cell derived extracellular vesicles as nanotherapeutics for concanavalin a induced hepatitis modulating the gut liver axis |
| topic | Extracellular vesicles Mesenchymal stromal cells Con A-induced hepatitis Gut microbiota |
| url | https://doi.org/10.1186/s13287-024-04013-7 |
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