Abstract
BACKGROUND: Mesenchymal stem cells, found in various tissues, possess significant healing and immunomodulatory properties, influencing macrophage polarization, which is essential for wound repair. However, chronic wounds present significant therapeutic challenges, requiring novel strategies to improve healing outcomes. AIM: To investigate the potential of fetal dermal mesenchymal stem cells (FDMSCs) in enhancing wound healing through modulation of macrophage polarization, specifically by promoting the M2 phenotype to address inflammatory responses in chronic wounds. METHODS: FDMSCs were isolated from BalB/C mice and co-cultured with RAW264.7 macrophages to assess their effects on macrophage polarization. Flow cytometry, quantitative reverse transcriptase polymerase chain reaction, and histological analyses were employed to evaluate shifts in macrophage phenotype and wound healing in a mouse model. Statistical analysis was performed using GraphPad Prism. RESULTS: FDMSCs induced macrophage polarization from the M1 to M2 phenotype, as demonstrated by a reduction in pro-inflammatory markers (inducible nitric oxide synthase, interleukin-6) and an increase in anti-inflammatory markers [mannose receptor (CD206), arginase-1] in co-cultured RAW264.7 macrophages. These shifts were confirmed by flow cytometry. In an acute skin wound model, FDMSC-treated mice exhibited faster wound healing, enhanced collagen deposition, and improved vascular regeneration compared to controls. Significantly higher expression of arginase-1 further indicated an enriched M2 macrophage environment. CONCLUSION: FDMSCs effectively modulate macrophage polarization from M1 to M2, reduce inflammation, and enhance tissue repair, demonstrating their potential as an immunomodulatory strategy in wound healing. These findings highlight the promising therapeutic application of FDMSCs in managing chronic wounds.