Dataset Information

Human Liver Stem Cell Transplantation Alleviates Liver Fibrosis in a Rat Model of CCl₄-Induced Liver Fibrosis.

ABSTRACT:

Background and objectives

Mesenchymal stem cells (MSCs) elicit therapeutic effects against liver fibrosis in animal models. Human liver stem cells (HLSCs) are cells isolated from human liver tissue that have mesenchymal morphology and express MSC markers. HLSCs also possess intrahepatic stem cell properties. We introduce a rat model of liver fibrosis and trans-portal transplantation of HLSC to demonstrate alleviation of liver fibrosis.

Methods and results

Liver fibrosis was induced by intraperitoneal injection of Carbon tetrachloride (CCl₄). Sprague Dawley rats underwent simultaneous partial hepatectomy of the left hepatic lobe and HLSC transplantation via the portal vein. Gross appearance of the liver observed following CCl₄ injection showed cholestasis and surface nodularity. Sirius red staining revealed deposition of collagen fibers in the extracellular matrix (ECM). Following HLSC transplantation, human albumin secreting cells were detected by immunohistochemistry in liver specimens. Quantitative measurements of fibrosis area stained by Sirius red were compared between baseline and post-HLSC transplant (1×10⁷ cells) following 10 weeks of CCl₄ treatment liver specimens. Fibrosis area (p<0.05), serum markers of liver inflammation and fibrosis (AST, ALT levels and APRI, p<0.05) significantly decreased from baseline after HLSC transplantation. RNA expression in liver tissues revealed significant decrease in tissue inhibitor of matrix metalloproteinase 1 (TIMP1), TIMP2 expression and increase in hepatocyte growth factor expression following HLSC transplantation (p<0.05).

Conclusions

HLSC transplantation effectively reduced the area of liver fibrosis with increased expression of factors promoting ECM degradation. These findings suggest the potential therapeutic role of HLSCs in various liver diseases presenting with liver fibrosis.

SUBMITTER: Lee JH

PROVIDER: S-EPMC8611308 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Acute liver injury (ALI) is a global health problem associated with high mortality and has attracted clinical attention. Ginkgo biloba extract (GBE) is an extract from dried Ginkgo leaves that has many pharmacological effects because of its various ingredients and has been shown to be hepatoprotective. We investigated the hepatoprotective effect of GBE on carbon tetrachloride (CCl4)-induced acute liver injury in vitro. The components of Ginkgo biloba extract are analyzed by LC-MS, and the key targets of "liver injury-Ginkgo biloba" are identified based on bioinformatics analysis. The signaling pathways such as PI3K/AKT are mainly enriched with high correlation in KEGG. The results of in vitro experiments showed that compared with the Model group, except that the ALT activity level and MDA content in EGB-L group were not significantly decreased (P > 0.05), the activity of ALT, AST and MDA content in other EGB groups were significantly decreased (P < 0.05), and the activities of SOD and CAT were significantly increased (P < 0.05). The expression of inflammatory factors IL-1β, IL-6 and TNF-α were also detected. The results showed that compared with the Model group, the contents of IL-6 in EGB-L group were not significantly decreased (P > 0.05), while the contents of IL-1β, IL-6 and TNF-α in other EGB groups were significantly decreased (P < 0.05), indicating that EGB could reduce the level of cell inflammation. Western blot assay detected the protein expression levels of GF, RTK, PI3K, AKT and p-AKT in cells. The results showed that compared with the Model group, the protein expression levels of GF, RTK, PI3K, AKT and P-AKT were significantly increased after EGB treatment (P < 0.05), and the protein expression level of the EGB-H group was higher than the EGB-L group. Ginkgo biloba extract can inhibit the expression of downstream related genes by activating PI3K/AKT signaling pathway, and at the same time alleviate the inflammatory response of cells, reduce the level of inflammation, and protect the cell damage caused by CCl4.

Dataset Information

Human Liver Stem Cell Transplantation Alleviates Liver Fibrosis in a Rat Model of CCl₄-Induced Liver Fibrosis.

Background and objectives

Methods and results

Conclusions

Similar Datasets

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Dataset Information

Human Liver Stem Cell Transplantation Alleviates Liver Fibrosis in a Rat Model of CCl4-Induced Liver Fibrosis.

Background and objectives

Methods and results

Conclusions

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Human Liver Stem Cell Transplantation Alleviates Liver Fibrosis in a Rat Model of CCl₄-Induced Liver Fibrosis.