Differentiation of Bone Marrow-derived Mesenchymal Stem Cells into Hepatocyte-like Cells on Nanofibers and Their Transplantation into a Carbon Tetrachloride-Induced Liver Fibrosis Model

2010 ◽  
Vol 7 (1) ◽  
pp. 103-118 ◽  
Author(s):  
Abbas Piryaei ◽  
Mojtaba Rezazadeh Valojerdi ◽  
Mansoureh Shahsavani ◽  
Hossein Baharvand
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Carbon Tetrachloride ◽  
Liver Fibrosis

scholarly journals Heterogenic transplantation of bone marrow-derived rhesus macaque mesenchymal stem cells ameliorates liver fibrosis induced by carbon tetrachloride in mouse

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e4336 ◽  
Author(s):  
Xufeng Fu ◽  
Bin Jiang ◽  
Bingrong Zheng ◽  
Yaping Yan ◽  
Junfeng Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Liver Transplantation ◽  
Mesenchymal Stem Cells ◽  
Carbon Tetrachloride ◽  
Liver Fibrosis ◽  
Liver Diseases ◽  
Pathological Examination ◽  
Paracrine Effects ◽  
End Stage

Liver fibrosis is a disease that causes high morbidity and has become a major health problem. Liver fibrosis can lead to the end stage of liver diseases (livercirrhosisand hepatocellularcarcinoma). Currently, liver transplantation is the only effective treatment for end-stage liver disease. However, the shortage of organ donors, high cost of medical surgery, immunological rejection and transplantation complications severely hamper liver transplantation therapy. Mesenchymal stem cells (MSCs) have been regarded as promising cells for clinical applications in stem cell therapy in the treatment of liver diseases due to their unique multipotent differentiation capacity, immunoregulation and paracrine effects. Although liver fibrosis improvements by MSC transplantation in preclinical experiments as well as clinical trials have been reported, the in vivo fate of MSCs after transportation and their therapeutic mechanisms remain unclear. In this present study, we isolated MSCs from the bone marrow of rhesus macaques. The cells exhibited typical MSC markers and could differentiate into chondrocytes, osteocytes, and adipocytes, which were not affected by labeling with enhanced green fluorescent protein (EGFP). The harvested MSCs respond to interferon-γ stimulation and have the ability to inhibit lymphocyte proliferation in vitro. EGFP-labeled MSCs (1 × 106 cells) were transplanted into mice with carbon tetrachloride-induced liver fibrosis via tail vein injection. The ability of the heterogenic MSC infusion to ameliorate liver fibrosis in mice was evaluated by a blood plasma chemistry index, pathological examination and liver fibrosis-associated gene expression. Additionally, a small number of MSCs that homed and engrafted in the mouse liver tissues were evaluated by immunofluorescence analysis. Our results showed that the transplantation of heterogenic MSCs derived from monkey bone marrow can be used to treat liver fibrosis in the mouse model and that the paracrine effects of MSCs may play an important role in the improvement of liver fibrosis.

scholarly journals Mesenchymal Stem Cells and Induced Bone Marrow-Derived Macrophages Synergistically Improve Liver Fibrosis in Mice

2018 ◽  
Vol 8 (3) ◽  
pp. 271-284 ◽  
Author(s):  
Yusuke Watanabe ◽  
Atsunori Tsuchiya ◽  
Satoshi Seino ◽  
Yuzo Kawata ◽  
Yuichi Kojima ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Liver Fibrosis

scholarly journals Ferulic Acid Induces Bone Marrow Mesenchymal Stem Cells to Alleviate the Activation of Hepatic Stellate Cells and Liver Fibrosis via Cytoskeletal Rearrangement Inhibition and Mir-19b-3p Transfer

2022 ◽  
Author(s):  
Rui Zhang ◽  
Wenhang Li ◽  
Xiandan Jiang ◽  
Xinyi Cui ◽  
Hongjie You ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Liver Fibrosis ◽  
Combination Therapy ◽  
Cytochalasin D ◽  
Specific Mechanism ◽  
Cytoskeletal Rearrangement ◽  
Marrow Mesenchymal Stem Cells

Abstract Background: Bone marrow mesenchymal stem cells (BMSCs) are effective for treating fibrotic liver. BMSCs contain a variety of proteins and RNAs, which have functions similar to their derived cells, but the specific mechanism is unclear. In a recent study, ferulic acid (FA) was highly effective in treating liver fibrosis. Therefore, we combined BMSCs and FA to treat CCl4-induced fibrosis models. Methods: First, we used BMSCs and FA to treat CCl4-induced fibrosis models and observed their therapeutic effect, investigated the specific mechanism of this combination therapy in liver fibrosis. Second, we created a BMSC/hepatic stellate cell (HSC) co-culture system and used FA to treat activated HSCs. We next used cytochalasin D and angiotensin II to investigate whether BMSCs and FA inactivate HSCs through cytoskeletal rearrangement. MiR-19b-3p was enriched in BMSCs and targeted TGF-β receptor II (TGF-βR2). We transfected miR-19b-3p into HSCs and BMSCs separately and detected whether BMSCs transferred miR-19b-3p to HSCs or inactivated HSCs. Results: We used BMSCs and FA to treat CCl4-induced fibrosis models and found that the combination therapy had better effects than FA or BMSCs alone. The expression of the profibrotic markers α-SMA and COL1-A1 was significantly decreased in HSCs co-cultured with BMSCs and FA treatment. Cytoskeletal rearrangement in HSCs was inhibited, and RhoA/ROCK pathway gene expression was decreased. With angiotensin II treatment, COL1-A1 and a-SMA expression increased, while with cytochalasin D treatment, profibrotic gene expression decreased in HSCs. COL1-A1, α-SMA and RhoA/ROCK pathway genes were decreased in activated HSCs treated with a miR-19b-3p mimic, indicating that miR-19b-3p inactivated HSCs by suppressing RhoA/ROCK signalling. In contrast, profibrotic genes were significantly decreased in BMSCs treated with the miR-19b-3p mimic or a miR-19b-3p inhibitor and FA compared with BMSCs treated with the miR-19b-3p mimic alone.Conclusion: BMSCs attenuated HSC activation and liver fibrosis by inhibiting cytoskeletal rearrangement and delivering miR-19b-3p to activated HSCs, inactivating RhoA/ROCK signaling. FA-based combination therapy showed better inhibitory effects on HSC activation, suggesting that BMSCs and their miRNAs combined with FA are novel antifibrotic therapeutics for treating chronic liver disease.

scholarly journals NADPH Oxidase Signaling Pathway Mediates Mesenchymal Stem Cell-Induced Inhibition of Hepatic Stellate Cell Activation

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Haowen Qiao ◽  
Yu Zhou ◽  
Xingping Qin ◽  
Jing Cheng ◽  
Yun He ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Liver Fibrosis ◽  
Nadph Oxidase ◽  
Signaling Pathway ◽  
Cell Activation ◽  
Stellate Cell ◽  
Smooth Muscle Actin ◽  
Alpha Smooth Muscle Actin

Background. Bone marrow-derived mesenchymal stem cells (BMSCs) have blossomed into an effective approach with great potential for the treatment of liver fibrosis. The aim of this study was to investigate the underlying antifibrosis mechanisms by which the BMSC inhibit activated hepatic stellate cells (HSCs) in vivo and in vitro. Methods. To study the effect of human bone marrow-derived mesenchymal stem cells (hBM-MSCs) on activated HSCs, we used HSCs and the coculture systems to evaluate the inhibition of activated HSCs from the aspects of the apoptosis of activated HSCs. In addition, activation of NADPH oxidase pathway and the changes in liver histopathology were tested by using the carbon tetrachloride- (CCl4-) induced liver fibrosis in mice. Results. Introduction of hBM-MSCs significantly inhibited the proliferation of activated HSCs by inducing the apoptosis process of activated HSCs. The effect of hBM-MSCs reduced the signaling pathway of NADPH oxidase in activated HSCs. Besides, the signaling pathway of NADPH oxidase mediated hBM-MSC upregulation of the expression of the peroxisome proliferator-activated receptor γ and downregulation of the expression of α1(I) collagen and alpha-smooth muscle actin (α-SMA) in activated HSCs. Moreover, the hBM-MSC-induced decrease in the signaling pathway of NADPH oxidase was accompanied by the decrease of the activated HSC number and liver fibrosis in a mouse model of CCl4-induced liver fibrosis. Conclusion. The hBM-MSCs act as a promising drug source against liver fibrosis development with respect to hepatopathy as a therapeutic target.

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