Liver epithelioid progenitor cells derived from fetal Luxi bovine alleviate liver fibrosis

ObjectiveLiver fibrosis and cirrhosis resulting from chronic liver injury represent a major healthcare burden worldwide. Growth differentiation factor (GDF) 11 has been recently investigated for its role in rejuvenation of ageing organs, but its role in chronic liver diseases has remained unknown. Here, we investigated the expression and function of GDF11 in liver fibrosis, a common feature of most chronic liver diseases.DesignWe analysed the expression of GDF11 in patients with liver fibrosis, in a mouse model of liver fibrosis and in hepatic stellate cells (HSCs) as well as in other liver cell types. The functional relevance of GDF11 in toxin-induced and cholestasis-induced mouse models of liver fibrosis was examined by in vivo modulation of Gdf11 expression using adeno-associated virus (AAV) vectors. The effect of GDF11 on leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5)+ liver progenitor cells was studied in mouse and human liver organoid culture. Furthermore, in vivo depletion of LGR5+ cells was induced by injecting AAV vectors expressing diptheria toxin A under the transcriptional control of Lgr5 promoter.ResultsWe showed that the expression of GDF11 is upregulated in patients with liver fibrosis and in experimentally induced murine liver fibrosis models. Furthermore, we found that therapeutic application of GDF11 mounts a protective response against fibrosis by increasing the number of LGR5+ progenitor cells in the liver.ConclusionCollectively, our findings uncover a protective role of GDF11 during liver fibrosis and suggest a potential application of GDF11 for the treatment of chronic liver disease.

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Comparative Study on Effect of Mesenchymal Stem Cells and Endothelial Progenitor Cells on Treatment of Experimental CCL4 Induced Liver Fibrosis

QJM ◽

10.1093/qjmed/hcaa051.006 ◽

2020 ◽

Vol 113 (Supplement_1) ◽

Author(s):

D Sabry ◽

W A Khalifa ◽

M M Abdelgwad ◽

M Alhelf ◽

Z M Altaib

Keyword(s):

Gene Expression ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Liver Fibrosis ◽

Liver Function ◽

Liver Regeneration ◽

Progenitor Cells ◽

Endothelial Progenitor Cells ◽

Treated Group ◽

Ki 67

Abstract Background Bone marrow mesenchymal stem cells (BM-MSCs) and human umbilical cord endothelial progenitor cells (UC-EPCs) have several benefits for liver regeneration. We speculate huge impacts of rat BM-MSCs and UC-EPCs on reversal of hepatic injury and improvement of liver function in liver fibrosis induced by carbon tetrachloride (CCl4). Methods Forty adult rats were divided into 4 groups; control group, CCl4 group, CCl4/BM-MSCs group and CCl4/UCEPCs group. Blood samples were driven from rats at 1, 2 and 3months to measure serum concentration of albumin and alanine aminotransferase (ALT). Quantitative expression of HGF,TGF-β, MMP-2, and VEGF were assessed by polymerase chain reaction. Histological examination of the liver tissue was performed. α-SMA immunohistochemistry to identify the myoepithelial cells (MECs) and Ki-67 to identify cell prolifration immunohistochemistry are detected in groups injected with cells to confirm cells regeneration. Results Regarding liver function, there was elevating albumin (P < 0.05) and reducing ALT (P < 0.05) concentrations in groups treated with BM-MSCs and UC-EPCs effect compared to untreated CCL4 group. Concerning gene expression, UC-EPCs treated group have significantly higher MMP-2 and VEGF (P < 0.01) genes expression than BM-MSCs treated group. Furthermore, UC-EPCs were more valuable than BM-MSCs in increasing gene expression of HGF (P < 0.05) and immunohistochemistry of α-SMA and Ki-67 (P < 0.01). BM-MSCs have significantly lower TGF- β (P < 0.00) compared to UC-EPCs. Conclusion This study highlighted on liver regeneration role of both human UC-EPCs and BM-MSCs in liver fibrosis by different signaling mechanistic.

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