Effect of human umbilical cord mesenchymal stem cells in treatment of mice with liver fibrosis and its mechanism

Pingji LIU; Lichao YAO; Xue HU; Zheng WANG; Zhiyu XIONG; Yingan JIANG

doi:10.12449/JCH240315

Volume 40 Issue 3

Mar. 2024

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Article Navigation > Journal of Clinical Hepatology > 2024 > 40(3): 527-532

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Effect of human umbilical cord mesenchymal stem cells in treatment of mice with liver fibrosis and its mechanism

DOI: 10.12449/JCH240315

Department of Infectious Diseases，Renmin Hospital of Wuhan University，Wuhan 430060，China

Research funding:

The Grant From the Anti-Aging Research Center, Wuhan University Education & Development Foundation (2002330);

The Fundamental Research Funds for the Central Universities (2042022kf1115)

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Corresponding author: JIANG Yingan， jiangya_cn@aliyun.com （ORCID： 0000-0003-4912-7494）
Received Date: 2023-06-09
Accepted Date: 2023-08-17
Published Date: 2024-03-20

Abstract

Abstract

Objective To investigate the effect of human umbilical cord mesenchymal stem cells （hUCMSCs） in the treatment of mice with liver fibrosis and its mechanism. Methods A total of 18 specific pathogen-free C57BL/6 mice， aged 6 weeks， were selected and divided into control group （n=6）， carbon tetrachloride （CCl₄） model group （CCl₄ group， n=6）， and hUCMSCs treatment group （MSC group， n=6） using a random number table. The mice in the CCl₄ group and the MSC group were given intraperitoneal injection of CCl₄ solution to establish a mouse model of liver fibrosis， while those in the control group were injected with the same dose of corn oil， and the mice in the MSC group were injected with hUCMSCs via the caudal vein during the injection of CCl₄. At the end of week 8， mouse serum was collected， and the mice were sacrificed to collect and fix the liver. Enzyme-linked immunosorbent assay was used to measure the levels of inflammatory factors； an automatic biochemical detector was used to measure liver function parameters； HE staining， Masson staining， Sirius Red staining， and α-SMA immunofluorescence assay were used to evaluate liver fibrosis. Hepatic stellate cells （HSCs） stimulated by TGF-β were co-cultured with hUCMSCs in the medium with or without chitinase-3 like-protein-1 （CHI3L1）， and Western blot was used to measure the expression levels of proteins. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the Dunnett’s t-test was used for further comparison between two groups. Results Masson staining and Sirius Red staining showed that the CCl₄ group had a significantly higher degree of fibrosis than the control group （both P<0.05）， and the MSC group had significant alleviation of fibrosis compared with the CCl₄ group （both P<0.05）. Compared with the control group， the CCl₄ group had significant increases in the levels of interleukin-1β， interleukin-6 （IL-6）， aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， and alkaline phosphatase （ALP）（all P<0.05）， and compared with the CCl₄ group， the MSC group had significant reductions in the levels of IL-6， AST， ALT， and ALP （all P<0.05）. The CCl₄ group had significantly higher expression levels of CHI3L1 and α-SMA than the control group and the MSC group （all P<0.05）. The cell culture experiment showed that the MSC+HSC group had a significantly higher expression level of Bax than the HSC group and the MSC+CHI3L1 group （both P<0.05）， suggesting that CHI3L1 reversed the pro-apoptotic effect of MSC on activated HSCs. Conclusion This study shows that hUCMSCs can improve liver fibrosis in mice， possibly by inhibiting CHI3L1 to promote the apoptosis of HSCs.
- Hepatic Fibrosis,
- Mesenchymal Stem Cells,
- Chitinase-3-Like Protein 1,
- Mice， Inbred C57BL

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References(15)

References

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Effect of human umbilical cord mesenchymal stem cells in treatment of mice with liver fibrosis and its mechanism

DOI: 10.12449/JCH240315

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Effect of human umbilical cord mesenchymal stem cells in treatment of mice with liver fibrosis and its mechanism

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