Stem cell research & therapy · 2025
Mesenchymal stromal cell-derived extracellular vesicles as nanotherapeutics for concanavalin a-induced hepatitis: modulating the gut‒liver axis.
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Yang Fan, Ni Beibei, Liang Xiaoqi, He Yizhan, Yuan Chao, Chu Jiajie, Huang Yiju, Zhong Hongyu, Yang Li, Lu Jianxi, Xu Yan, Zhang Qi, Chen Wenjie
Аннотация
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.
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.