Adipose-derived stem cell extracellular vesicles attenuate liver fibrosis via restoration of gut barrier function and modulation of gut microbiota

作者：Baitong Wu, Jingyi Guo, Jian Wang, Jiuxing Feng, Jun Xu · 发表于：Extracellular Vesicles and Circulating Nucleic Acids · 年份：2025 · DOI：10.20517/evcna.2025.95 · 被引用次数：3 · 研究领域：Extracellular vesicles in disease、Liver physiology and pathology、Tissue Engineering and Regenerative Medicine

Aim: Liver fibrosis (LF) is a major pathological stage that may progress to end-stage chronic liver injury but currently lacks effective treatment strategies. Previous studies have shown that adipose-derived stem cell extracellular vesicles (ADSC-EVs) play crucial roles in tissue repair, immune regulation, and anti-inflammatory effects. This study aims to elucidate the therapeutic effect of ADSC-EVs in LF and reveal their regulation mechanisms in gut-liver axis dysregulation. Methods: The LF mouse model was established by intraperitoneal injection of diethylnitrosamine/CCl<sub>4</sub>. LF mice for ADSC-EV treatment received ADSC-EVs (200 μg per mouse) twice a week for three weeks. Then, hepatic function tests, liver and gut histopathology, and gut microbiota analyses were performed. Results: ADSC-EVs effectively improved hepatic function, reduced collagen deposition and suppressed hepatic stellate cell activation, exhibiting potent anti-fibrotic potential in LF mice. Additionally, they significantly restored intestinal barrier integrity by reducing intestinal permeability and reinforcing the mucus barrier. Furthermore, ADSC-EV treatment regulated gut microbiota dysbiosis, increased the abundance of beneficial intestinal bacteria such as Akkermansia muciniphila. ADSC-EV intervention also elevated the level of butyric acid in cecal contents and significantly reduced systemic inflammation. Conclusion: Our findings suggest that ADSC-EVs represent a promising novel the...