• hP-MSC therapy effectively ameliorates PSC in Mdr2−/− mice, as evidenced by improved liver histology, reduced liver enzymes, and decreased inflammatory factors.
• Serum metabolomics identified 41 differentially expressed metabolites, with key pathways involving bile acid metabolism, lipid metabolism, and hydroxyproline metabolism.
• Eight serum metabolites were identified as potential efficacy biomarkers, with four decreasing and four increasing after hP-MSC treatment, offering non-invasive monitoring options.
• The study provides preclinical evidence supporting the therapeutic potential of hP-MSCs for PSC and highlights metabolic regulatory mechanisms underlying their efficacy.