Erythropoietin-overexpressing mesenchymal stem cells accelerate diabetic wound healing via steroid signaling pathway modulation

Figure 7 Schematic illustration of the proposed mechanism by which erythropoietin-overexpressing mesenchymal stem cells enhance diabetic wound healing. Erythropoietin-overexpressing mesenchymal stem cells are locally injected around full-thickness skin wounds in leptin receptor-deficient mice, resulting in enhanced wound closure. Integrated multi-omics analysis (bulk RNA sequencing, proteomics, and single-cell RNA sequencing) identifies a serum amyloid A3-positive macrophage subset as a key effector population. Erythropoietin-overexpressing mesenchymal stem cells strengthen C-C motif chemokine ligand-centered signaling from serum amyloid A3-positive macrophages to neutrophils, which promotes angiogenesis and modulates inflammation to improve tissue repair. EPO: Erythropoietin; MSC: Mesenchymal stem cell; Saa3: Serum amyloid A3; CCL: C-C motif chemokine ligand; db/db: Leptin receptor-deficient diabetic mouse.