scholarly journals Exosomes Derived from Human Umbilical Cord Mesenchymal Stem Cells Alleviate Liver Fibrosis

2013 ◽  
Vol 22 (6) ◽  
pp. 845-854 ◽  
Author(s):  
Tingfen Li ◽  
Yongmin Yan ◽  
Bingying Wang ◽  
Hui Qian ◽  
Xu Zhang ◽  
...  
2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Qing Zhou ◽  
Tengfei Gu ◽  
Yong Zhang ◽  
Hongda Li ◽  
Xuemei Zhuansun ◽  
...  

Mesenchymal stem cells (MSCs) were shown to have potential therapeutic effects for treatment of liver fibrosis, and dysregulated expression of microRNAs (miRNAs) played a pivotal role in the pathogenesis of liver fibrosis by regulating their downstream target genes. However, the mechanism by which MSCs affect the progression of liver fibrosis by regulating miRNA expression remains unclear. Here, we investigated whether human umbilical cord MSCs (HUC-MSCs) attenuated hepatic fibrosis by regulating miR-455-3p and its target gene. Significantly upregulated miRNA (miR-455-3p) was screened out by GEO datasets analysis and coculture HUC-MSCs with hepatic stellate cell (HSC) LX-2 cells. p21-activated kinase-2 (PAK2) was forecasted to be the target gene of miR-455-3p by bioinformatics analyses and confirmed by luciferase reporter assay. HUC-MSCs were transplanted into mice with carbon tetrachloride- (CCl4-) induced liver fibrosis, the result showed that HUC-MSC transplantation significantly ameliorated the severity of CCl4-induced liver fibrosis, attenuated collagen deposition, improved liver function by reducing the expression of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum, upregulated miR-455-3p, and suppressed PAK2 expression of liver tissue in mice. Taken together, our study suggests that HUC-MSCs inhibit the activation of HSCs and mouse CCl4-induced liver fibrosis by upregulation of miR-455-3p through targeting PAK2.


2021 ◽  
Author(s):  
Yang Li ◽  
Xueshuai Ye ◽  
Xueqian Zhang ◽  
Ziqi Cai ◽  
Li Shen ◽  
...  

Abstract Background: Umbilical cord mesenchymal stem cells (UC-MSCs) transplantation have become a promising treatment for liver fibrosis. However, UC-MSCs have limited anti-fibrosis ability, and their homing ability of UC-MSCs to the injured liver sites appears to be poor. In this study, we aimed to determining if overexpression of CXCL9 could have the synergistic anti-fibrosis effect with UC-MSCs, and whether it can promote the homing ability of UC-MSCs.Methods: Overexpression of CXCL9 in UC-MSCs (CXCL9-UC-MSCs) was attained by transfection of naive UC-MSCs with the lenti-CXCL9-mCherry. The impact of transplanted CXCL9-UC-MSCs on both repairing of liver fibrosis and homing was evaluated and compared with lenti-mCherry empty vector transfected UC-MSCs (control UC-MSCs).Results: After puromycin screening, UC-MSCs could stably express CXCL9 without affecting the stem and differentiation ability of UC-MSCs. In addition, biochemical analysis showed that the liver function of CXCL9-UC-MSCs was significantly increased in comparison with that of control UC-MSCs (P < 0.05). Futhermore, histopathology after 4 weeks of cell therapy demonstrated that the content of collagen fibers decreased obviously, the pseudo-lobules almost disappeared, and the morphology of hepatic lobules was basically normal. Frozen sections were performed 24 hours and 4 weeks after the cell injection. It can be seen that the fluorescence expression of the CXCL9-UC-MSCs group was significantly higher than that of the control UC-MSCs group, which proved that CXCL9-UC-MSCs have a stronger chemotactic ability, and can stay longer than control UC-MSCs in the injured liver.Conclusion: Overexpression of CXCL9 improves the efficacy of UC-MSC therapy for liver fibrosis repair, thereby promoting the homing and staying of UC-MSCs to injured hepatic sites in a rat model of liver fibrosis.


Toxin Reviews ◽  
2019 ◽  
pp. 1-12 ◽  
Author(s):  
Alireza Pouyandeh Ravan ◽  
Farjam Goudarzi ◽  
Hassan Rafieemehr ◽  
Mahdi Bahmani ◽  
Fariba Rad ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document