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

2020 ◽  
Author(s):  
Xia Yao ◽  
Jing Wang ◽  
Jiajing Zhu ◽  
Xiaoli Rong
Keyword(s):  
Stem Cells ◽  
Liver Fibrosis ◽  
Epithelial Mesenchymal Transition ◽  
Therapeutic Potential ◽  
Fetal Skin ◽  
Mesenchymal Transition ◽  
Cell Based Therapy ◽  
Current Therapies ◽  
Causes Of Mortality

Abstract 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.

Human fetal skin-derived stem cell secretome reduce liver fibrosis

2020 ◽  
Author(s):  
Xia Yao ◽  
Jing Wang ◽  
Jiajing Zhu ◽  
Xiaoli Rong
Keyword(s):  
Stem Cells ◽  
Liver Fibrosis ◽  
Epithelial Mesenchymal Transition ◽  
Therapeutic Potential ◽  
Fetal Skin ◽  
Mesenchymal Transition ◽  
Cell Based Therapy ◽  
Current Therapies ◽  
Causes Of Mortality

Abstract 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.

scholarly journals Anti-fibrotic effect of human fetal skin-derived stem cell secretomeon the liver fibrosis

2020 ◽  
Author(s):  
Xia Yao ◽  
Jing Wang ◽  
Jiajing Zhu ◽  
Xiaoli Rong
Keyword(s):  
Stem Cells ◽  
Liver Fibrosis ◽  
Epithelial Mesenchymal Transition ◽  
Therapeutic Potential ◽  
Fetal Skin ◽  
Mesenchymal Transition ◽  
Cell Based Therapy ◽  
Current Therapies ◽  
Causes Of Mortality

Abstract 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.

scholarly journals The Anti-fibrotic Effect of Human Fetal Skin-derived Stem Cell Secretome on the Liver Fibrosis

2020 ◽  
Author(s):  
Xia Yao ◽  
Jing Wang ◽  
Jiajing Zhu ◽  
Xiaoli Rong
Keyword(s):  
Stem Cells ◽  
Liver Fibrosis ◽  
Epithelial Mesenchymal Transition ◽  
Therapeutic Potential ◽  
Fetal Skin ◽  
Mesenchymal Transition ◽  
Cell Based Therapy ◽  
Causes Of Mortality ◽  
Smad7 Expression

Abstract Background: Liver fibrosis resulting from chronic liver injury is one of the major causes of mortality worldwide. Stem cells-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 ofhuman fetal skin-derived stem cells (hFFSCs) secretome in the treatment of liver fibrosis. To determine the therapeutic potential of the hFFSCssecretome in liver fibrosis, we established the CCl4-induced rat liver fibrosis model, and administered hFFSCssecretome in vivo. Moreover, we investigated the anti-fibrotic mechanism of hFFSCssecretome in hepatic stellate cells (HSCs).Results: Our results showed that hFFSCssecretomeffectively reduced collagen content in liver, improved the liver function and promoted liver regeneration. Interestingly, we also found thathFFSCssecretom reduced liver fibrosis through suppressing the epithelial-mesenchymal transition (EMT) process. In addition, we found that hFSSCsecretom inhibited the TGF-β1, Smad2, Smad3, and Collagen I expression, however, increased Smad7 expression.Conclusions: In conclusions, our results suggest that hFFSCssecretome treatment could reduce CCl4-induced liver fibrosis via regulating the TGF-β/Smad signal pathway.

scholarly journals Human fetal skin-derived stem cell secretome reduce liver fibrosis by regulating TGF-β/Smad signal pathway

2020 ◽  
Author(s):  
Xia Yao ◽  
Jing Wang ◽  
Jiajing Zhu ◽  
Xiaoli Rong
Keyword(s):  
Stem Cells ◽  
Liver Fibrosis ◽  
Therapeutic Potential ◽  
Signal Pathway ◽  
Fetal Skin ◽  
Cell Based Therapy ◽  
Causes Of Mortality ◽  
Smad7 Expression ◽  
Rat Liver Fibrosis

Abstract Background: Liver fibrosis resulting from chronic liver injury is one of the major causes of mortality worldwide. Stem cells-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 cells (hFFSCs) secretome in the treatment of liver fibrosis. To determine the therapeutic potential of the hFFSCs secretome in liver fibrosis, we established the CCl4-induced rat liver fibrosis model, and administered hFFSCs secretome in vivo. Moreover, we investigated the anti-fibrotic mechanism of hFFSCs secretome in hepatic stellate cells (HSCs). Results: Our results showed that hFFSCs secretom effectively reduced collagen content in liver, improved the liver function and promoted liver regeneration. In addition, we found that hFSSC secretom inhibited the TGF-β1, Smad2, Smad3, and Collagen I expression, however, increased Smad7 expression. Conclusions: In conclusions, our results suggest that hFFSCs secretome treatment could reduce CCl4-induced liver fibrosis via regulating the TGF-β/Smad signal pathway.

scholarly journals 3D hESC exosomes enriched with miR-6766-3p ameliorates liver fibrosis by attenuating activated stellate cells through targeting the TGFβRII-SMADS pathway

2021 ◽  
Author(s):  
Ning Wang ◽  
Xiajing Li ◽  
Zhiyong Zhong ◽  
Yaqi Qiu ◽  
Shoupei Liu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Liver Fibrosis ◽  
Liver Injury ◽  
Cell Activation ◽  
Therapeutic Potential ◽  
Stellate Cell ◽  
Embryonic Stem ◽  
Luciferase Reporter ◽  
Fibrotic Liver

Abstract BackgroundExosomes secreted from stem cells exerted salutary effects on the fibrotic liver. Herein, the roles of exosomes derived from human embryonic stem cell (hESC) in anti-fibrosis were extensively investigated. Compared with two-dimensional (2D) culture, the clinical and biological relevance of three-dimensional (3D) cell spheroids were greater because of their higher regeneration potential since they behave more like cells in vivo. In our study, exosomes derived from 3D human embryonic stem cells (hESC) spheroids and the monolayer (2D) hESCs were collected and compared the therapeutic potential for fibrotic liver in vitro and in vivo. ResultsIn vitro, PKH26 labled-hESC-Exosomes were shown to be internalized and integrated into TGFβ-activated-LX2 cells, and reduced the expression of profibrogenic markers, thereby regulating cellular phenotypes. TPEF imaging indicated that PKH26-labled-3D-hESC-Exsomes possessed an enhanced capacity to accumulate in the livers and exhibited more dramatic therapeutic potential in the injured livers of fibrosis mouse model. 3D-hESC-Exosomes decreased profibrogenic markers and liver injury markers, and improved the level of liver functioning proteins, eventually restoring liver function of fibrosis mice. miRNA array revealed a significant enrichment of miR-6766-3p in 3D-hESC-Exosomes, moreover, bioinformatics and dual luciferase reporter assay identified and confirmed the TGFβRII gene as the target of miR-6766-3p. Furthermore, the delivery of miR-6766-3p into activated-LX2 cells decreased cell proliferation, chemotaxis and profibrotic effects, and further investigation demonstrated that the expression of target gene TGFβRII and its downstream SMADs proteins, especially phosphorylated protein p-SMAD2/3 was also notably down-regulated by miR-6766-3p. These findings unveiled that miR-6766-3p in 3D-hESC-Exosomes inactivated SMADs signaling by inhibiting TGFβRII expression, consequently attenuating stellate cell activation and suppressing liver fibrosis. ConclusionsOur results showed that miR-6766-3p in the 3D-hESC-Exosomes inactivates smads signaling by restraining TGFβRII expression, attenuated LX2 cell activation and suppressed liver fibrosis, suggesting that 3D-hESC-Exosome enriched-miR6766-3p is a novel anti-fibrotic therapeutics for treating chronic liver disease. These results also proposed a significant strategy that 3D-Exo could be used as natural nanoparticles to rescue liver injury via delivering antifibrotic miR-6766-3p.

scholarly journals Insights into Differentiation of Melanocytes from Human Stem Cells and Their Relevance for Melanoma Treatment

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2508
Author(s):  
Madalina Mirea ◽  
Stefan Eckensperger ◽  
Markus Hengstschläger ◽  
Mario Mikula
Keyword(s):  
Stem Cells ◽  
Cell Differentiation ◽  
Developmental Process ◽  
Epithelial Mesenchymal Transition ◽  
Stem Cell Differentiation ◽  
Human Stem Cells ◽  
Mesenchymal Transition ◽  
Melanocytic Differentiation

Malignant melanoma represents a highly aggressive form of skin cancer. The metastatic process itself is mostly governed by the so-called epithelial mesenchymal transition (EMT), which confers cancer cells migrative, invasive and resistance abilities. Since EMT represents a conserved developmental process, it is worthwhile further examining the nature of early developmental steps fundamental for melanocyte differentiation. This can be done either in vivo by analyzing the physiologic embryo development in different species or by in vitro studies of melanocytic differentiation originating from embryonic human stem cells. Most importantly, external cues drive progenitor cell differentiation, which can be divided in stages favoring neural crest specification or melanocytic differentiation and proliferation. In this review, we describe ectopic factors which drive human pluripotent stem cell differentiation to melanocytes in 2D, as well as in organoid models. Furthermore, we compare developmental mechanisms with processes described to occur during melanoma development. Finally, we suggest differentiation factors as potential co-treatment options for metastatic melanoma patients.

scholarly journals Mesenchymal Stem Cells Pretreated with HGF and FGF4 Can Reduce Liver Fibrosis in Mice

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Sulaiman Shams ◽  
Sadia Mohsin ◽  
Ghazanfar Ali Nasir ◽  
Mohsin Khan ◽  
Shaheen N. Khan
Keyword(s):  
Stem Cells ◽  
Liver Fibrosis ◽  
Liver Injury ◽  
Therapeutic Potential ◽  
Direct Injection ◽  
Glycogen Storage ◽  
Pretreated Group ◽  
Mouse Hepatocytes

Stem cells have opened a new avenue to treat liver fibrosis. We investigated in vitro and in vivo the effect of cytokine (HGF and FGF4) pretreated MSCs in reduction of CCl4liver injury. Mouse MSCs were pretreated with cytokines to improve their ability to reduce CCl4injury. In vitro we gave CCl4injury to mouse hepatocytes and cocultured it with untreated and cytokines pretreated MSCs. For in vivo study we labeled MSCs with PKH-26 and transplanted them into CCl4injured mice by direct injection into liver. In vitro data showed that cytokines pretreated MSCs significantly reduce LDH level and apoptotic markers in CCl4injured hepatocytes cocultured model. Furthermore the cytokines pretreated MSCs also improved cell viability and enhanced hepatic and antiapoptotic markers in injured hepatocytes cocultured model as compared to untreated MSCs. In vivo data in cytokines pretreated group demonstrated greater homing of MSCs in liver, restored glycogen storage, and significant reduction in collagen, alkaline phosphatase, and bilirubin levels. TUNEL assay and real time PCR also supported our hypothesis. Therefore, cytokines pretreated MSCs were shown to have a better therapeutic potential on reduction of liver injury. These results demonstrated the potential utility of this novel idea of cytokines pretreated MSCs for the treatment of liver fibrosis.

Mechanism of chronic aristolochic acid nephropathy: role of Smad3

2010 ◽  
Vol 298 (4) ◽  
pp. F1006-F1017 ◽  
Author(s):  
Li Zhou ◽  
Ping Fu ◽  
Xiao Ru Huang ◽  
Fei Liu ◽  
Arthur C. K. Chung ◽  
...  
Keyword(s):  
Transforming Growth Factor ◽  
Aristolochic Acid ◽  
Epithelial Mesenchymal Transition ◽  
Therapeutic Potential ◽  
Critical Role ◽  
Chronic Administration ◽  
Mesenchymal Transition ◽  
Aristolochic Acid Nephropathy

Aristolochic acid nephropathy (AAN) has become a worldwide disease and is the most severe complication related to the use of traditional Chinese medicine. However, the pathogenic mechanisms of AAN remain unclear and therapies are limited. The present study tested the hypothesis that transforming growth factor (TGF)-β/Smad3 may be a key pathway leading to chronic AAN. This was examined in vivo in Smad3 wild-type/knockout (WT/KO) mice and in vitro in tubular epithelial cells with knockdown of Smad2 or Smad3. Results revealed that chronic administration of aristolochic acid (AA) resulted in a severe AAN characterized by progressive renal dysfunction and tubulointerstitial fibrosis including epithelial-mesenchymal transition (EMT) in Smad3 WT mice, but not in Smad3 KO mice, suggesting a critical role for Smad3 in the development of AAN. This was further tested in vitro. We found that AA was able to activate Smad signaling to mediate EMT and renal fibrosis via both TGF-β-dependent and JNK/MAP kinase-dependent mechanisms because blockade of JNK and specific knockdown of Smad3, but not Smad2, were able to attenuate AA-stimulated collagen matrix expression and EMT. In conclusion, TGF-β/Smad3 may be an essential mediator for chronic AAN. Results from this study indicate that specific blockade of the TGF-β/Smad3 signaling pathway may have therapeutic potential for chronic AAN.

scholarly journals In vivo hepatogenic capacity and therapeutic potential of stem cells from human exfoliated deciduous teeth in liver fibrosis in mice

2015 ◽  
Vol 6 (1) ◽  
Author(s):  
Takayoshi Yamaza ◽  
Fatima Safira Alatas ◽  
Ratih Yuniartha ◽  
Haruyoshi Yamaza ◽  
Junko K. Fujiyoshi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Liver Fibrosis ◽  
Therapeutic Potential ◽  
Deciduous Teeth ◽  
Human Exfoliated Deciduous Teeth

scholarly journals Bortezomib limits renal allograft interstitial fibrosis by inhibiting NF-κB/TNF-α/Akt/mTOR/P70S6K/Smurf2 pathway via IκBα protein stabilization

2021 ◽  
Vol 135 (1) ◽  
pp. 53-69
Author(s):  
Chuanjian Suo ◽  
Zeping Gui ◽  
Zijie Wang ◽  
Jiajun Zhou ◽  
Ming Zheng ◽  
...  
Keyword(s):  
Renal Allograft ◽  
Epithelial Mesenchymal Transition ◽  
Therapeutic Potential ◽  
Interstitial Fibrosis ◽  
Protein Stabilization ◽  
Mesenchymal Transition ◽  
P70s6 Kinase ◽  
Tnf Α

Abstract Chronic allograft dysfunction is a major cause of late graft failure after kidney transplantation. One of the histological changes is interstitial fibrosis, which is associated with epithelial–mesenchymal transition. Bortezomib has been reported to prevent the progression of fibrosis in organs. We used rat renal transplantation model and human kidney 2 cell line treated with tumor necrosis factor-α (TNF-α) to examine their response to bortezomib. To explore the mechanism behind it, we assessed the previously studied TNF-α/protein kinase B (Akt)/Smad ubiquitin regulatory factor 2 (Smurf2) signaling and performed RNA sequencing. Our results suggested that bortezomib could attenuate the TNF-α-induced epithelial–mesenchymal transition and renal allograft interstitial fibrosis in vitro and in vivo. In addition to blocking Akt/mammalian target of rapamycin (mTOR)/p70S6 kinase/Smurf2 signaling, bortezomib’s effect on the epithelial–mesenchymal transition was associated with inhibition of nuclear factor kappa B (NF-κB) pathway by stabilizing inhibitor of NF-κB. The study highlighted the therapeutic potential of bortezomib on renal allograft interstitial fibrosis. Such an effect may result from inhibition of NF-κB/TNF-α/Akt/mTOR/p70S6 kinase/Smurf2 signaling via stabilizing protein of inhibitor of NF-κB.

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