Characterization of PBMC secretome: Iron-quercetin preconditioning enhances pro-angiogenic and tissue regeneration factors for potential autologous diabetic wound healing applications

Impaired wound healing, particularly in diabetic and chronic wounds, remains a significant global health challenge. While current therapies show promise, their effectiveness is often constrained by high costs, limited accessibility, and inconsistent outcomes across patient populations. This study investigates the potential of the Iron-Quercetin complex (IronQ) to enhance the regenerative secretory profile of peripheral blood mononuclear cells (PBMCs), with the aim of developing a cost-effective, cell-free therapeutic approach. PBMCs isolated from both healthy and diabetic donors were preconditioned with IronQ for 10 days. The resulting secretomes were analyzed for their protein and metabolic profiles, focusing on pro-angiogenic and immunomodulatory factors. In vitro assays were performed to assess the effects of IronQ-preconditioned secretomes on the proliferation, migration, and collagen production of endothelial cells, fibroblasts, and keratinocytes. IronQ preconditioning significantly enriched PBMC secretomes with cytokines such as TGF-α, TNF-α, IL-6, IL-10, HGF, G-CSF, M-CSF, GM-CSF, and GRO-α, along with enhanced glycolytic activity and the production of bioactive metabolites. Furthermore, these secretomes promoted the proliferation and migration of endothelial cells, fibroblasts, and keratinocytes, as well as collagen production by fibroblasts, with consistent effects observed across both healthy and diabetic donors. Collectively, these findings support the potential of IronQ-preconditioned PBMC secretomes as a scalable, autologous, and cost-effective alternative to current cell-based therapies for diabetic wound healing, warranting further in vivo and clinical evaluation.