Iron–quercetin complex induces ex vivo proteomic remodeling in circulating proangiogenic cells derived from human peripheral blood mononuclear cells

Iron(III)-quercetin complex (IronQ) has previously been shown to support the ex vivo expansion of peripheral blood mononuclear cell (PBMC)-derived proangiogenic cells with CAC-like features, enable MRI-based cell tracking, and enhance proangiogenic activity. However, the intracellular proteomic changes associated with IronQ treatment remained uncharacterized. In this study, we aimed to define the intracellular protein programs of IronQ-treated PBMC-derived CAC-like proangiogenic adherent cells at days 7, 14, and 21 using LC-MS/MS-based quantitative proteomics, with targeted validation of selected proteins as an exploratory ex vivo model. IronQ treatment was associated with significant upregulation of ferritin heavy chain (FTH1) and ferritin light chain (FTL), consistent with intracellular iron sequestration. Stress-response and exocytosis-related proteins were concurrently downregulated, suggesting adaptive maintenance of cellular homeostasis during prolonged culture. Pathway analysis identified stage-specific upregulation of proteins implicated in vascular development at day 7 (8 proteins) and day 14 (14 proteins), including regulators of cell migration, blood vessel morphogenesis, and extracellular matrix remodeling. Overall, these findings provide a proteomic framework for understanding IronQ-mediated proangiogenic cell conditioning and identify candidate protein targets for subsequent functional validation.