BACKGROUND: Vascular insufficiency is associated with the pathogenesis and therapeutic outcomes of diabetic foot ulcers (DFU). While mesenchymal stem cells (MSCs) hold potential for DFU treatment, further enhancement in promoting angiogenesis in the challenging DFU wounds is imperative. METHODS: The differential expression of pro- and anti-angiogenic factors during both normal and diabetic wound healing was compared using quantitative PCR. MSCs derived from the umbilical cord was prepared, and the engineered MSC (MSC RESULTS: The comprehensive analysis of the temporal expression of pro- and anti-angiogenic factors revealed a consistent impairment in ANG1 expression throughout diabetic wound healing. MSC CONCLUSION: Treatment with MSCs alone promotes angiogenesis and DFU healing, while the engineering of MSCs with ANG1 provides substantial additional benefits to this therapeutic process. The engineering of MSCs with ANG1 presents a promising avenue for developing innovative strategies in managing DFU.