Department of Anesthesiology, The Affiliated Hospital of Changchun University of Chinese Medicine, 1478 Gongnong Road, Changchun, 130021, Jilin, China.
Department of Gynecology, The Affiliated Hospital of Changchun University of Chinese Medicine, 1478 Gongnong Road, Changchun, 130021, Jilin, China.
Stem Cell Res Ther. 2020 Sep 3;11(1):379. doi: 10.1186/s13287-020-01891-5.
Liver fibrosis resulting from chronic liver injury is one of the major causes of mortality worldwide. Stem cell-secreted secretome has been evaluated for overcoming the limitations of cell-based therapy in hepatic disease, while maintaining its advantages.
In this study, we investigated the effect of human fetal skin-derived stem cell (hFSSC) secretome in the treatment of liver fibrosis. To determine the therapeutic potential of the hFSSC secretome in liver fibrosis, we established the CCl-induced rat liver fibrosis model and administered hFSSC secretome in vivo. Moreover, we investigated the anti-fibrotic mechanism of hFSSC secretome in hepatic stellate cells (HSCs).
Our results showed that hFSSC secretome effectively reduced collagen content in liver, improved the liver function and promoted liver regeneration. Interestingly, we also found that hFSSC secretome reduced liver fibrosis through suppressing the epithelial-mesenchymal transition (EMT) process. In addition, we found that hFSSC secretome inhibited the TGF-β1, Smad2, Smad3, and Collagen I expression, however, increased the Smad7 expression.
In conclusions, our results suggest that hFSSC secretome treatment could reduce CCl-induced liver fibrosis via regulating the TGF-β/Smad signal pathway.
慢性肝损伤导致的肝纤维化是全球范围内主要的致死原因之一。干细胞分泌的分泌物已被评估用于克服肝疾病中基于细胞的治疗的局限性,同时保持其优势。
在这项研究中,我们研究了人胎儿皮肤来源的干细胞(hFSSC)分泌物在治疗肝纤维化中的作用。为了确定 hFSSC 分泌物在肝纤维化中的治疗潜力,我们建立了 CCl 诱导的大鼠肝纤维化模型,并在体内给予 hFSSC 分泌物。此外,我们研究了 hFSSC 分泌物在肝星状细胞(HSCs)中的抗纤维化机制。
我们的结果表明,hFSSC 分泌物可有效减少肝脏中的胶原含量,改善肝功能并促进肝再生。有趣的是,我们还发现 hFSSC 分泌物通过抑制上皮-间充质转化(EMT)过程来减少肝纤维化。此外,我们发现 hFSSC 分泌物抑制 TGF-β1、Smad2、Smad3 和 Collagen I 的表达,然而,增加了 Smad7 的表达。
总之,我们的结果表明,hFSSC 分泌物通过调节 TGF-β/Smad 信号通路,可减少 CCl 诱导的肝纤维化。