Department of Clinical Laboratory, China-Japan Union Hospital of Jilin University, 126 Xiantai St., Changchun, 130033, Jilin, China.
The Scientific Research Center, China-Japan Union Hospital of Jilin University, 126 Xiantai St., Changchun, 130033, Jilin, China.
Stem Cell Res Ther. 2019 Mar 18;10(1):98. doi: 10.1186/s13287-019-1204-2.
Mesenchymal stem cells (MSCs) are increasingly being applied as a therapy for liver fibrosis. Exosomes possess similar functions to their parent cells; however, they are safe and effective cell-free reagents with controllable and predictable outcomes. In this study, we investigated the therapeutic potential and underlying molecular mechanism for human bone mesenchymal stem cells-derived exosomes (hBM-MSCs-Ex) in the treatment of liver fibrosis.
We established an 8-week CCl-induced rat liver fibrosis model, after which, we administered hBM-MSCs-Ex in vivo for 4 weeks. The resulting histopathology, liver function, and inflammatory cytokines were analyzed. In addition, we investigated the anti-fibrotic mechanism of hBM-MSCs-Ex in hepatic stellate cells (HSCs) and liver fibrosis tissue, by western blotting for the expression of Wnt/β-catenin signaling pathway-related genes.
In vivo administration of hBM-MSCs-Ex effectively alleviated liver fibrosis, including a reduction in collagen accumulation, enhanced liver functionality, inhibition of inflammation, and increased hepatocyte regeneration. Moreover, based on measurement of the collagen area, Ishak fibrosis score, MDA levels, IL-1, and IL-6, the therapeutic effect of hBM-MSCs-Ex against liver fibrosis was significantly greater than that of hBM-MSCs. In addition, we found that hBM-MSCs-Ex inhibited the expression of Wnt/β-catenin pathway components (PPARγ, Wnt3a, Wnt10b, β-catenin, WISP1, Cyclin D1), α-SMA, and Collagen I, in both HSCs and liver fibrosis tissue.
These results suggest that hBM-MSCs-Ex treatment could ameliorate CCl-induced liver fibrosis via inhibition of HSC activation through the Wnt/β-catenin pathway.
间充质干细胞（MSCs）越来越多地被应用于肝纤维化的治疗。外泌体具有与其亲本细胞相似的功能；然而，它们是安全有效的无细胞试剂，具有可控和可预测的结果。在这项研究中，我们研究了人骨髓间充质干细胞衍生的外泌体（hBM-MSCs-Ex）在治疗肝纤维化中的治疗潜力和潜在的分子机制。
我们建立了一个 8 周的 CCl 诱导的大鼠肝纤维化模型，之后在体内给予 hBM-MSCs-Ex 治疗 4 周。分析了由此产生的组织病理学、肝功能和炎症细胞因子。此外，我们通过 Western blot 检测 Wnt/β-catenin 信号通路相关基因的表达，研究了 hBM-MSCs-Ex 在肝星状细胞（HSCs）和肝纤维化组织中的抗纤维化机制。
体内给予 hBM-MSCs-Ex 可有效减轻肝纤维化，包括胶原积累减少、肝功能增强、炎症抑制和肝细胞再生增加。此外，根据胶原面积、Ishak 纤维化评分、MDA 水平、IL-1 和 IL-6 的测量，hBM-MSCs-Ex 治疗肝纤维化的疗效明显优于 hBM-MSCs。此外，我们发现 hBM-MSCs-Ex 抑制了 HSCs 和肝纤维化组织中 Wnt/β-catenin 途径成分（PPARγ、Wnt3a、Wnt10b、β-catenin、WISP1、Cyclin D1）、α-SMA 和 Collagen I 的表达。
这些结果表明，hBM-MSCs-Ex 通过抑制 Wnt/β-catenin 通路抑制 HSC 激活，可改善 CCl 诱导的肝纤维化。
