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 CCl4-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 CCl4-induced liver fibrosis via inhibition of HSC activation through the Wnt/β-catenin pathway.

Background: When the deer antler is cast, it leaves a cutaneous wound that can achieve scarless healing due to the presence of antler stem cells (ASCs). This provides an opportunity to study regenerative wound healing. Methods: In this study, we investigated the therapeutic effects and mechanism of antler stem cell-conditioned medium (ASC-CM) on cutaneous wound healing in rats. In vitro, we investigated the effects of the ASC-CM on proliferation of HUVEC and NIH-3T3 cell lines. In vivo, we evaluated the effects of ASC-CM on cutaneous wound healing using full-thickness skin punch-cut wounds in rats. Results: The results showed that ASC-CM significantly stimulated proliferation of the HUVEC and NIH-3T3 cells in vitro. In vivo, completion of healing of the rat wounds treated with ASC-CM was on day 16 (± 3 days), 9 days (± 2 days) earlier than the control group (DMEM); the area of the wounds treated with ASC-CM was significantly smaller (p < 0.05) than the two control groups. Further molecular characterization showed that the ratios of Col3A1/Col1A2, TGF-β3/TGF-β1, MMP1/TIMP1, and MMP3/TIMP1 significantly increased (p < 0.01) in the healed tissue in the ASC-CM group. Conclusions: In conclusion, ASC-CM effectively accelerated the wound closure rate and enhanced the quality of healing, which might be through transforming wound dermal fibroblasts into the fetal counterparts. Therefore, the ASC-CM may have potential to be developed as a novel cell-free therapeutic for scarless wound healing.

Background: Radiation dermatitis is a refractory skin injury caused by radiotherapy. Human fetal skin-derived stem cell (hFSSC) is a preferable source for cell therapy and skin tissue regeneration. In the present study, we investigated the repair effect of using hFSSC secretome on a radiation skin injury model in rats. Methods: We prepared the hFSSC secretome and studied its effects on the proliferation and tube formation of human umbilical vein endothelial cell (HUVEC) in vitro. Furthermore, we used a Sr-90 radiation-induced skin injury model of rats and evaluated the effects of hFSSC secretome on radiation skin injury in vivo. Results: The results showed that hFSSC secretome significantly promoted the proliferation and tube formation of HUVEC in vitro; in addition, hFSSC secretome-treated rats exhibited higher healing quality and faster healing rate than the other two control groups; the expression level of collagen type III α 1 (Col3A1), transforming growth factor β3 (TGF-β3), angiotensin 1 (Ang-1), angiotensin 2 (Ang-2), vascular endothelial growth factor (VEGF), and placental growth factor (PLGF) was significantly increased, while collagen type I α 2 (Col1A2) and transforming growth factor β1 (TGF-β1) were decreased in hFSSC secretome group. Conclusions: In conclusion, our results provided the first evidence on the effects of hFSSC secretome towards radiation-induced skin injury. We found that hFSSC secretome significantly enhanced radiation dermatitis angiogenesis, and the therapeutic effects could match with the characteristics of fetal skin. It may act as a kind of novel cell-free therapeutic approach for radiation-induced cutaneous wound healing.

Radiation-induced cutaneous injury is the main side effect of radiotherapy. The injury is difficult to cure and the pathogenesis is complex. Mesenchymal stem cells (MSCs) serve as a promising candidate for cell-based therapy for the treatment of cutaneous wounds. The aim of the present study was to investigate whether antler stem cells (AnSCs) have better therapeutic effects on radiation-induced cutaneous injury than currently available ones. In this study, a rat model of cutaneous wound injury from Sr-90 radiation was used. AnSCs (1 × 10⁶/500 μl) were injected through the tail vein on the first day of irradiation. Our results showed that compared to the control group, AnSC-treated rats exhibited a delayed onset (14 days versus 7 days), shorter recovery time (51 days versus 84 days), faster healing rate (100% versus 70% on day 71), and higher healing quality with more cutaneous appendages regenerated (21:10:7/per given area compared to those of rat and human MSCs, respectively). More importantly, AnSCs promoted much higher quality of healing compared to other types of stem cells, with negligible scar formation. AnSC lineage tracing results showed that the injected-dye-stained AnSCs were substantially engrafted in the wound healing tissue, indicating that the therapeutic effects of AnSCs on wound healing at least partially through direct participation in the wound healing. Expression profiling of the wound-healing-related genes in the healing tissue of AnSC group more resembled a fetal wound healing. Revealing the mechanism underlying this higher quality of wound healing by using AnSC treatment would help to devise more effective cell-based therapeutics for radiation-induced wound healing in clinics.

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.

Background: Liver fibrosis resulting from a chronic liver injury is one of the significant causes of mortality. Stem cells-secreted secretome has been evaluated for overcoming the limitations of cell-based therapy in hepatic disease while maintaining its advantages over the current therapies.Methods: In this study, we investigated the effect of human fetal skin-derived stem cells (hFSSCs) secretome in the treatment of liver fibrosis. To determine the therapeutic potential of the hFSSCs secretome in liver fibrosis, we established the CCl₄-induced liver fibrosis rat model, and we administered hFSSCs secretome in vivo. Moreover, we investigated the anti-fibrotic mechanism of hFSSCs secretome in hepatic stellate cells (HSCs). Results: Our results showed that hFSSCs secretome effectively reduced collagen content in the liver, and improved the liver function and promoted liver regeneration. Interestingly, we also found that hFSSCs 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, while we observed, increased Smad7 expression. Conclusions: In conclusion, our results suggest that hFSSCs secretome treatment could reduce CCl₄-induced liver fibrosis via regulating the TGF-β/Smad signal pathway.