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Therapeutic Potential of Mesenchymal Stem Cells in Reversing Hepatic Cellular Injury via Anti-Inflammatory and Anti-Apoptotic Mechanisms

Ana Paula Rodrigues, PhD1, Rafael Henrique Costa, PhD, Mariana Luiza Fernandes, PhD ORCID *

1 Center for Experimental Hepatology and Translational Research, School of Medicine, University of Campinas (UNICAMP), Campinas, Brazil.

DOI: 10.18081/2378-5225/14.98  
Cited by 0

 Article history: Received 10 August 2025 · Revised 09 September 2025 · Accepted 22 September 2025 · Published 01 October 2025

© 2025 Fernandes, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (CC BY 4.0). 

CC BY 4.0                                                                                                   

Abstract

Background: Hepatic cellular injury is a central pathological feature of acute and chronic liver diseases and is driven by sustained inflammation, oxidative stress, and activation of apoptotic pathways. Despite advances in supportive and disease-specific therapies, effective strategies capable of reversing established liver injury remain limited. Mesenchymal stem cells (MSCs) have emerged as promising regenerative agents due to their immunomodulatory and cytoprotective properties.

Methods: Hepatic injury was induced in rats by repeated administration of carbon tetrachloride (CCl₄). Animals were treated with intravenous MSCs, fibroblast control cells, or saline. Liver function was assessed by serum biochemical analysis. Histopathological evaluation, cytokine profiling, flow cytometry, gene expression analysis, and assessment of apoptosis and oxidative stress were performed to elucidate cellular and molecular mechanisms underlying MSC-mediated effects.

Results: MSC therapy significantly reduced serum alanine aminotransferase and aspartate aminotransferase levels and partially restored albumin concentrations compared with untreated injured animals. Histological analysis revealed preservation of hepatic architecture and reduced inflammatory infiltration following MSC administration. MSC treatment markedly suppressed pro-inflammatory cytokines while enhancing anti-inflammatory mediators and promoted a shift toward a reparative macrophage phenotype. Hepatocyte apoptosis was significantly reduced, as evidenced by decreased TUNEL positivity, lower caspase activity, and modulation of mitochondrial apoptotic signaling proteins. Additionally, MSC therapy alleviated oxidative stress by reducing lipid peroxidation and restoring endogenous antioxidant defenses. Tracking studies demonstrated limited hepatic engraftment of MSCs, supporting a predominantly paracrine mechanism of action.

Conclusion: Mesenchymal stem cell therapy effectively attenuates hepatic cellular injury through coordinated anti-inflammatory, anti-apoptotic, and antioxidant mechanisms. By modulating the hepatic injury microenvironment rather than relying on long-term engraftment, MSCs promote hepatocyte survival and structural preservation. These findings provide mechanistic support for the continued development of MSC-based regenerative strategies for liver disease.

Keywords: Mesenchymal stem cells; Hepatic cellular injury; Liver regeneration; Inflammation; Apoptosis; Oxidative stress.

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BM-Publisher · Pathophysiology of Cell Injury Journal (PCIJ) · E-ISSN 2378-5225 · DOI Prefix 10.18081/pcij/2378-5225

Pathophysiology of Cell Injury Journal (PCIJ)
E-ISSN 2378-5225 · Biannual
BM-Publisher (London, UK)
Open Access

Vol 14, Issue 2 (October 2025), pp. 120–139

Rodrigues AR, Costa RH, Fernandes M. Therapeutic Potential of Mesenchymal Stem Cells in Reversing Hepatic Cellular Injury via Anti-Inflammatory and Anti-Apoptotic Mechanisms. Pathophysiology of Cell Injury Journal (PCIJ). 2025;14(2):98–119. doi: 10.18081/2378-5225/14.120.

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(2025) . Pathophysiology of Cell Injury Journal (PCIJ), , pp. . Available at: https://pcij.net/archives/2229
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