Adipose-derived mesenchymal stem cells mitigate methotrexate-induced liver cirrhosis (fibrosis) model

O. Sorgun, O. Erbaş

Department of Emergency Medicine, Sağlık Bilimleri University Tepecik Training and Research Hospital, Izmir, Turkey. omay.sorgun@saglik.gov.tr

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• Hepatology

OBJECTIVE: Hepatic fibrosis is a severe liver condition characterized by abnormal fibroblast activity, excessive extracellular matrix deposition, inflammation, and structural alterations. Methotrexate (MTX), a pharmaceutical agent widely used for its therapeutic properties, is known to induce hepatotoxicity. However, the precise mechanisms underlying MTX-induced liver injury remain elusive. This study investigates the therapeutic potential of Adipose-Derived Mesenchymal Stem Cells (ADMSCs) in alleviating MTX-induced liver injury in a rat model.

MATERIALS AND METHODS: Thirty male Wistar albino rats were employed in this study. Liver injury was induced in twenty rats by a single MTX dose, while ten rats constituted the control group. The MTX group was further subdivided into two cohorts, one receiving ADMSC treatment and the other saline solution. The treatment duration was 14 days. ADMSCs, isolated from adipose tissue, were characterized by CD13, CD29, and CD105 markers. Biomarker analysis, histopathological evaluations, and various measurements were conducted to assess ADMSCs’ therapeutic efficacy.

RESULTS: MTX administration significantly increased Transforming Growth Factor-β (TGF-β), Platelet-Derived Growth Factor (PDGF), Plasma Cytokeratin 18, Plasma Malondialdehyde (MDA), and Liver MDA levels, with histopathological liver damage. ADMSC treatment notably lowered TGF-β, PDGF, Plasma Cytokeratin 18, Plasma MDA, and Liver MDA levels, accompanied by reduced liver damage observed histologically. Liver Enzyme ALT levels were also reduced in the MTX and ADMSC groups compared to the MTX and Saline groups.

CONCLUSIONS: ADMSCs exhibit significant potential in ameliorating MTX-induced liver injury, with notable anti-oxidative and anti-apoptotic properties. These findings suggest that ADMSCs may effectively mitigate oxidative stress and inflammation associated with MTX-induced liver damage. Further research is essential to investigate the clinical application of ADMSCs in liver disease management and uncover the underlying therapeutic mechanisms.

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