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Cited by 7Mesenchymal stem cell researchLiver physiology and pathologyLiver Disease and Transplantation

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Mesenchymal stem cell therapy for liver fibrosis need “partner”: Results based on a meta-analysis of preclinical studies

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Xu, Yan, Wang, Xue-Song, Zhou, Xiao-Lei, Lu, Wen-Ming, Tang, Xing-Kun, Jin, Yu, Ye, Jun-Song·2024·World Journal of Gastroenterology
DOI 10.3748/wjg.v30.i32.3766PMC PMC11362880
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Abstract

BACKGROUND The efficacy of mesenchymal stem cells (MSCs) in treating liver fibrosis has been demonstrated in several clinical studies. However, their low survival and liver implantation rates remain problematic. In recent years, a large number of studies in animal models of liver fibrosis have shown that MSCs combined with drugs can improve the efficacy of MSCs in the treatment of liver fibrosis alone and inhibit its progression to end-stage liver disease. This has inspired new ways of thinking about treating liver fibrosis. AIM To investigate the effectiveness and mechanisms of MSCs combined with drugs in treating liver fibrosis. METHODS Data sources included four electronic databases and were constructed until January 2024. The subjects, interventions, comparators, outcomes, and study design principle were used to screen the literature, and the quality of the literature was evaluated to assess the risk of bias. Relevant randomised controlled trials were selected, and the final 13 studies were included in the final study. RESULTS A total of 13 studies were included after screening. Pooled analysis showed that MSCs combined with drug therapy significantly improved liver function, promoted the repair of damaged liver tissues, reduced the level of liver fibrosis-related indexes, and effectively ameliorated hepatic fibrosis by modulating the hepatic inflammatory microenvironment, promoting the homing of MSCs, and regulating the relevant signaling pathways, and the treatment efficacy was superior to MSCs alone. However, the combined treatment statistics showed no ame-lioration in serum albumin levels (standardized mean difference = 0.77, 95% confidence interval: -0.13 to 1.68, P = 0.09). CONCLUSION In conclusion, MSCs combined with drugs for treating liver fibrosis effectively make up for the shortcomings of MSCs in their therapeutic effects. However, due to the different drugs, the treatment mechanism and effect also differ. Therefore, more randomized controlled trials are needed to compare the therapeutic efficacy of different drugs in combination with MSCs, aiming to select the “best companion” of MSCs in treating hepatic fibrosis.

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Figure 1 Literature selection and inclusion process. RCT: Randomized control trial.
Figure 1 Literature selection and inclusion process. RCT: Randomized control trial.CC BY-NC · PubMed Central
Figure 2 Risk of bias graph and bias summary. A: Review authors’ judgments about each risk of bias item presented as percentages across all included studies; B: Review authors’ judgments about each risk of bias item for each included study.
Figure 2 Risk of bias graph and bias summary. A: Review authors’ judgments about each risk of bias item presented as percentages across all included studies; B: Review authors’ judgments about each risk of bias item for each included study.CC BY-NC · PubMed Central
Figure 3 Forest plots. A: Aspartate aminotransferase (AST); B: Mesenchymal stem cells source subgroups of AST levels; C: Animal model subgroup of AST levels; D: Mechanism subgroup of AST levels; E: Alanine aminotransferase (ALT); F: Mechanism subgroup of ALT levels; G and H: Hydroxyproline; I: Forest plot of type III collagen; J: Mechanism subgroup of transforming growth factor beta gene levels. MSCs: Mesenchymal stem cells; 95%CI: 95% confidence interval; BM-MSCs: Bone marrow mesenchymal stem cells; AT-MSCs: Adipose mesenchymal stem cells; PD-MSCs: Placental mesenchymal stem cells.
Figure 3 Forest plots. A: Aspartate aminotransferase (AST); B: Mesenchymal stem cells source subgroups of AST levels; C: Animal model subgroup of AST levels; D: Mechanism subgroup of AST levels; E: Alanine aminotransferase (ALT); F: Mechanism subgroup of ALT levels; G and H: Hydroxyproline; I: Forest plot of type III collagen; J: Mechanism subgroup of transforming growth factor beta gene levels. MSCs: Mesenchymal stem cells; 95%CI: 95% confidence interval; BM-MSCs: Bone marrow mesenchymal stem cells; AT-MSCs: Adipose mesenchymal stem cells; PD-MSCs: Placental mesenchymal stem cells.CC BY-NC · PubMed Central
Figure 4 Sensitivity analysis. A: Aspartate aminotransferase; B: Alanine aminotransferase; C: Hydroxyproline; D: Transforming growth factor-β; E: Type Ⅲ collagen; F: Masson staining.
Figure 4 Sensitivity analysis. A: Aspartate aminotransferase; B: Alanine aminotransferase; C: Hydroxyproline; D: Transforming growth factor-β; E: Type Ⅲ collagen; F: Masson staining.CC BY-NC · PubMed Central
Figure 5 Funnel plot and Egger’s publication bias plot. A: Funnel plot with pseudo-95% confidence limits [aspartate aminotransferase (AST)]; B: Egger’s publication bias plot (AST); C: Funnel plot with pseudo-95% confidence limits [alanine aminotransferase (ALT)]; D: Egger’s publication bias plot (ALT). SMD: Standardized mean difference.
Figure 5 Funnel plot and Egger’s publication bias plot. A: Funnel plot with pseudo-95% confidence limits [aspartate aminotransferase (AST)]; B: Egger’s publication bias plot (AST); C: Funnel plot with pseudo-95% confidence limits [alanine aminotransferase (ALT)]; D: Egger’s publication bias plot (ALT). SMD: Standardized mean difference.CC BY-NC · PubMed Central
Figure 6 Diagram of the mechanism of mesenchymal stem cell therapy for liver fibrosis. MSCs: Mesenchymal stem cells; HSCs: Hepatic stellate cells.
Figure 6 Diagram of the mechanism of mesenchymal stem cell therapy for liver fibrosis. MSCs: Mesenchymal stem cells; HSCs: Hepatic stellate cells.CC BY-NC · PubMed Central

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Metadata

Authors
Xu, Y., Wang, X.-S., Zhou, X.-L., Lu, W.-M., Tang, X.-K., Jin, Y., & Ye, J.-S.
Affiliations
Gannan Medical University (CN)
ORCID
Xu, Yan
Venue
World Journal of Gastroenterology
Publisher
Baishideng Publishing Group Inc.
Published
2024-08-28
Volume
30
Issue
32
Pages
3766-3782
ISSN
1007-9327 (ISSN-L)
DOI
10.3748/wjg.v30.i32.3766
PMC
PMC11362880
OpenAlex
W4401871416
Cited by
7
References
8
Citations by year
2026: 4 · 2025: 3
FWCI
0.53
Type
journal article
Language
en
Open access
Licence
cc-by-nc
Locations
  • World Journal of Gastroenterology (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Mesenchymal stem cell research
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
  • Health Sciences › Medicine › Hepatology › Liver Disease and Transplantation
Keywords
mesenchymal stem cells, liver fibrosis, combination therapy, stem cell homing, liver inflammation, liver regeneration, serum albumin, end-stage liver disease, animal models
MeSH terms
Animals, Combined Modality Therapy, Disease Models, Animal, Humans, Liver, Liver Cirrhosis, Randomized Controlled Trials as Topic, Treatment Outcome, Disease Progression, Mesenchymal Stem Cell Transplantation, Mesenchymal Stem Cells

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