Department of Veterinary Surgery, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, 611130, China.
Sichuan Jinbei Banshan Group Co Ltd, Chengdu, 610041, China.
Stem Cell Res Ther. 2024 Oct 24;15(1):378. doi: 10.1186/s13287-024-03988-7.
Liver fibrosis is a common pathological process of chronic liver disease, characterized by excessive deposition of extracellular matrix (ECM). Mesenchymal stem cells (MSCs) have been found to have potential therapy effect on liver fibrosis, but the mechanism involved was still unclear. The objective of this study is to investigate the therapeutic efficacy of adipose-derived mesenchymal stem cells (ADMSCs) on the treatment of liver fibrosis, with particular emphasis on elucidating the underlying mechanism of action through which ADMSCs inhibit the activation of hepatic stellate cells (HSCs).
ADMSCs were isolated from adipose tissue and injected intravenously into hepatic fibrosis model of rats. The histopathological changes, liver function, collagen deposition, the expression of fibroin and Hippo pathway were evaluated. In vitro, ADMSCs were co-cultured with HSCs activated by transforming growth factor beta (TGF-β), and the inhibitor of Hippo pathway was used to evaluate the therapeutic mechanism of ADMSCs transplantation.
The results showed that after the transplantation of ADMSCs, the liver function of rats was improved, the degree of liver fibrosis and collagen deposition were reduced, and the Hippo signaling pathway was activated. In vitro, ADMSCs can effectively inhibit the proliferation and activation of HSCs induced by TGF-β treatment. However, the inhibitory effect of ADMSCs was weakened after blocking the Hippo signaling pathway.
ADMSCs inhibit HSCs activation by regulating YAP/TAZ, thereby promoting functional recovery after liver fibrosis. These findings lay a foundation for further investigation into the precise mechanism by which ADMSCs alleviate liver fibrosis.
肝纤维化是慢性肝病的一种常见病理过程，其特征是细胞外基质（ECM）过度沉积。间充质干细胞（MSCs）已被发现对肝纤维化具有潜在的治疗作用，但具体的作用机制仍不清楚。本研究旨在探讨脂肪来源间充质干细胞（ADMSCs）治疗肝纤维化的疗效，并特别强调通过 ADMSCs 抑制肝星状细胞（HSCs）活化来阐明其作用机制。
从脂肪组织中分离 ADMSCs，并静脉注射到肝纤维化大鼠模型中。评估组织病理学变化、肝功能、胶原沉积、纤维蛋白表达和 Hippo 通路。体外，将 ADMSCs 与转化生长因子β（TGF-β）激活的 HSCs 共培养，并使用 Hippo 通路抑制剂评估 ADMSCs 移植的治疗机制。
结果表明，ADMSCs 移植后，大鼠肝功能改善，肝纤维化程度和胶原沉积减少，Hippo 信号通路被激活。体外，ADMSCs 可有效抑制 TGF-β处理诱导的 HSCs 的增殖和活化。然而，阻断 Hippo 信号通路后，ADMSCs 的抑制作用减弱。
ADMSCs 通过调节 YAP/TAZ 抑制 HSCs 的活化，从而促进肝纤维化后的功能恢复。这些发现为进一步研究 ADMSCs 缓解肝纤维化的确切机制奠定了基础。
