The anti-fibrotic effect of human fetal skin-derived stem cell secretome on the liver fibrosis
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RESEARCH
Open Access
The anti-fibrotic effect of human fetal skinderived stem cell secretome on the liver fibrosis Xia Yao1, Jing Wang2, Jiajing Zhu3 and Xiaoli Rong4,5*
Abstract 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 CCl4-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 CCl4-induced liver fibrosis via regulating the TGF-β/Smad signal pathway. Keywords: hFSSC, Secretome, Liver fibrosis, TGF-β/Smad
Introduction Liver fibrosis is a wound healing response generated against chronic or iterative liver injury [1]. Recent evidence suggests that stem cell-based liver fibrosis treatment can be mediated through paracrine effects [2, 3]. The exclusive use of stem cell-secreted secretome has been evaluated for overcoming the limitations of cell-based therapy, while maintaining its advantages to their parent cells [4]. * Correspondence: [email protected]; [email protected] 4 Department of Clinical Laboratory, The Affiliated Hospital of Changchun University of Chinese Medicine, 1478 Gongnong Road, Changchun 130021, Jilin, China 5 Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA Full list of author information is available at the end of the article
It included extracellular vesicles and other soluble proteins or biologically active molecules. In addition, previous studies have indicated that human bone marrow mesenchymal stem cell-derived exosomes and other stem cellderived secretome can reduce liver fibrosis [5, 6]. Previous studies have indicated that the features of fetal tissue cells facilitate engraftment in vivo and may provide preferred effects against diseases difficult to treat [7]. Since 1928, hundreds of clinical trials using various types of fetal transplants have been performed worldwide [8–10]. Moreover, recent studies have demonstrated that human fetal stem cells (FSCs) have a gre
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