FGFR2 is a Crucial Factor for Adipose‐Derived Mesenchymal Stem Cells in Promoting Diabetic Foot Ulcer Healing Through Angiogenesis

ABSTRACT Diabetic foot ulcers (DFUs) remain a significant clinical challenge due to the lack of effective treatments, severely impacting patients' quality of life. Mesenchymal stem cells (MSCs) have shown potential in promoting DFU healing; however, the underlying mechanisms are not yet fully understood. This study investigates the role of adipose‐derived mesenchymal stem cells (ADSCs) in DFU healing, with a particular focus on angiogenesis. Gene expression profiles from the GSE7014 and GSE80178 datasets in the Gene Expression Omnibus (GEO) database were analyzed. Differentially expressed genes (DEGs) were intersected with angiogenesis‐related genes from the GeneCards database, identifying 35 angiogenesis‐related DEGs (An‐DEGs). Key genes were selected using Cytoscape software and machine learning. The pro‐angiogenic effects of ADSCs were validated through in vivo and in vitro experiments, assessing their role in DFU healing. The DEGs from DFU patients were enriched in pathways such as angiogenesis and collagen‐containing extracellular matrix. ADSCs promoted angiogenesis and wound healing by upregulating FGFR2 and secreting FGF, activating the FGF‐PI3K/Akt‐HIF‐1α‐VEGF axis. Additionally, ADSCs mediated secretion of VEGF concerting this effect. FGFR2 plays a pivotal role in ADSCs' mediated DFU healing by driving angiogenesis.