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Background  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.    Methods  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 4 -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).    Results  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.    Conclusions  In conclusions, our results suggest that hFSSC secretome treatment could reduce CCl 4 -induced liver fibrosis via regulating the TGF-β/Smad signal pathway.

The anti-fibrotic effect of human fetal skin-derived stem cell secretome on the liver fibrosis