Combined Mesenchymal Stem Cells and Metformin Therapy Modulates Key Macromolecular Pathways in Pulmonary Fibrosis: Evidence from Untargeted Metabolomics

ABSTRACT:

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial lung disease. Current treatment options remain limited, driving interest in novel therapeutic approaches. Mesenchymal stem cells (MSCs) possess immunomodulatory and regenerative properties, while metformin, traditionally used for type 2 diabetes, has recently demonstrated anti-fibrotic potential through its effects on cellular metabolism. Metabolomic profiling provides a comprehensive strategy to explore disease-associated biochemical alterations and therapeutic mechanisms. In this pilot study, pulmonary fibrosis was induced in rats using bleomycin. Animals were then treated with MSCs, metformin, or both. Plasma and lung tissue underwent untargeted LC-MS-based metabolomic analysis, supported by histopathological examination of lung architecture. Combination therapy resulted in the most substantial correction of metabolite disturbances, notable improvements observed in the levels of argininosuccinic acid, lysophosphatidylcholine (18:0/0:0), cytidine diphosphate, 5-hydroxyindoleacetic acid, and chenodeoxycholic acid, reflecting restored to nitrogen balance, lipid metabolism, nucleotide biosynthesis, serotonin turnover, and bile acid signaling. PCA showed distinct clustering of the combination group near controls, while histology confirmed nearcomplete resolution of fibrosis. These findings provide preliminary evidence that combined MSCs and metformin therapy exerts synergistic effects on fibrotic and metabolic pathways. Identified metabolite alterations may serve as potential early biomarkers for disease progression and therapeutic response

INSTRUMENT(S): Liquid Chromatography MS - negative - reverse phase, Liquid Chromatography MS - positive - reverse phase

PROVIDER: MTBLS12893 | MetaboLights | 2025-08-25

REPOSITORIES: MetaboLights