Adipose-Derived Mesenchymal Stem Cells Accelerate Diabetic Foot Ulcer Healing by Promoting Macrophage M2 Polarization Through Downregulation of EREG and CSTA .

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Purpose Macrophage polarization plays a critical role in the chronic wound healing of diabetic foot ulcers (DFU). Recent studies have shown that adipose-derived mesenchymal stem cells (ADSCs) can reduce inflammation in DFU and promote wound healing. Despite advances in stem cell therapy, the molecular mechanisms by which ADSCs regulate macrophage polarization in DFU healing remain unclear, and robust prognostic models for DFU are lacking. This study aims to identify macrophage polarization-associated molecules in DFU and explore whether ADSCs promote DFU healing by regulating these molecules. Patients and methods Macrophage polarization-associated differentially expressed genes (MA-DEGs) were screened from GSE134431 and GSE80178 datasets. Protein-protein interaction (PPI) networks were constructed using STRING and Cytoscape. Machine learning and Firth regression were employed to develop a prognostic model, which was evaluated using receiver operating characteristic (ROC) curves. The expression of predicted genes ( EREG and CSTA ) and the regulatory effects of ADSCs on these genes were validated in both DFU mouse model and THP-1 cells. Results A total of 30 macrophage polarization-associated differentially expressed genes (MA-DEGs) were identified, including 18 hub genes. These MA-DEGs were primarily enriched in pathways related to leukocyte chemotaxis and interleukin-4 and 13.

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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