Background Chronic atrophic gastritis (CAG), a prevalent gastrointestinal disorder, is characterized by gastric mucosal atrophy and increased cancer risk. Mesenchymal stem cells (MSCs) exhibit immunomodulatory, anti‐inflammatory, and tissue‐regenerative properties; however, their therapeutic potential for CAG remains underexplored. Methods A rat CAG model was established using a multifactor induction protocol. Animals received weekly intravenous administrations of MSCs or MSC‐conditioned medium (MSC‐CM) for 4 weeks. Post‐treatment, gastric antral tissues were subjected to histopathological analysis, cytokine microarray, transcriptomics, proteomics, untargeted metabolomics, and lipidomics. Subsequently, the expression of CXCL9, CXCL10, and CXCL11 in the rat gastric antrum was verified by qPCR, and the expression of CDK1 protein was verified by Western blotting. In vitro validation was performed in IFN‐γ‐stimulated THP‐1 macrophages treated with MSC‐CM. Results At 20 weeks post‐modeling, significant mucosal atrophy was observed in the rat gastric antrum. H&E staining confirmed that both MSC and MSC‐CM treatments ameliorated histopathological atrophy. Cytokine microarray revealed downregulation of nine inflammatory mediators: G‐CSF, GM‐CSF, IFN‐γ, IL‐6, IL‐10, IL‐13, IL‐17α, M‐CSF, and MCP‐1. Multi‐omics and experimental data demonstrated aberrant upregulation of Cxcl9 / Cxcl10 / Cxcl11 , Cdk1, and D‐ribose in the CAG group, all significantly suppressed by MSC and MSC‐CM therapy. In THP‐1 cells, MSC‐CM dose‐dependently reduced CXCL9/CXCL10/CXCL11 and IL-6 expression. Conclusions MSCs likely exert their therapeutic efficacy against CAG primarily through paracrine mechanisms. Mechanistically, MSCs coordinately target the “CXCL9/CXCL10/CXCL11‐CDK1‐D‐ribose” axis to suppress inflammation and restore gastric mucosal atrophy.
Bai et al. (Thu,) studied this question.