间充质基质细胞衍生的细胞外囊泡作为伴刀豆球蛋白A诱导性肝炎的纳米治疗剂：调节肠-肝轴

Mesenchymal stromal cell-derived extracellular vesicles as nanotherapeutics for concanavalin a-induced hepatitis: modulating the gut‒liver axis.

作者信息

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

机构信息

Biotherapy Centre, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510630, P.R. China.

Xinjiang Stem Cells Special Plateau Disease Engineering Technology Research Center, The First People's Hospital of Kashi, The Affiliated Kashi Hospital of Sun Yat-Sen University), Kashi, 844000, P.R. China.

出版信息

Stem Cell Res Ther. 2025 Jan 7;16(1):4. doi: 10.1186/s13287-024-04013-7.

DOI:10.1186/s13287-024-04013-7

PMID:39773662

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11706160/

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.

摘要

背景

作为无细胞纳米疗法，间充质干细胞衍生的细胞外囊泡（MSC-EVs）已显示出对肝脏疾病的潜在治疗作用。然而，它们对自身免疫性肝炎（AIH）的影响尚未完全明确。

方法与结果

在本研究中，我们利用成熟的刀豆蛋白A（Con A）诱导的暴发性肝炎小鼠模型来研究MSC-EVs对AIH的影响。我们发现，MSC-EVs对C57BL/6雄性小鼠Con A诱导的肝炎具有显著的保护作用，其有效性严重依赖于肠道微生物群。MSC-EVs调节肠道微生物群的组成，特别是通过增加无分类地位的Muribaculaceae科的丰度，并影响肝脏代谢谱，从而显著改善肝损伤。将乙酰-DL-缬氨酸鉴定为一种保护性代谢物，突出了针对肠道-肝脏轴相互作用在肝脏疾病治疗中的潜在治疗价值。