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