Serum metabonomics reveal the effectiveness of human placental mesenchymal stem cell therapy for primary sclerosing cholangitis

作者：Yingduo Yu, Qigu Yao, Deying Chen, Zhehua Zhang, Qiaoling Pan, Jiong Yu, Hongcui Cao, Liang Li, ­Jun Li­ · 发表于：Stem Cell Research & Therapy · 年份：2024 · DOI：10.1186/s13287-024-03967-y · 被引用次数：4 · 研究领域：Liver Diseases and Immunity、Liver physiology and pathology、Liver Disease Diagnosis and Treatment

BACKGROUND: The metabolic patterns of human placental-derived mesenchymal stem cell (hP-MSC) treatment for primary sclerosing cholangitis (PSC) remain unclear, and therapeutic effects significantly vary due to individual differences. Therefore, it is crucial to investigate the serological response to hP-MSC transplantation through small molecular metabolites and identify easily detectable markers for efficacy evaluation. METHODS: C-dansylation and DmPA labeling LC-MS analysis to investigate changes in metabolic pathways after hP-MSC treatment. Key metabolites and regulatory enzymes were validated by qRT-PCR and Western blotting. Potential biomarkers of hP-MSC efficacy were identified through correlation analysis and machine learning. RESULTS: Collectively, the results of the liver histology, serum liver enzyme levels, and inflammatory factors supported the therapeutic efficacy of hP-MSC treatment. Based on significant differences, 41 differentially expressed metabolites were initially identified; these were enriched in bile acid, lipid, and hydroxyproline metabolism. After treatment, bile acid transport was accelerated, whereas bile acid production was reduced; unsaturated fatty acid synthesis was upregulated overall, with increased FADS2 and elongase expression and enhanced fatty acid β-oxidation; hepatic proline 4-hydroxylase expression was decreased, leading to reduced hydroxyproline production. Correlation analysis of liver enzymes and metabolites, combined with time tren...