Combination of Hypoxia-Preconditioned ADSCs and Deferoxamine Can Speed Up the Healing of Diabetic Wounds by Promoting Angiogenesis and Regulating Macrophage Polarization.

Transplanting hypoxic prestimulated adipose-derived stem cells (ADSCs) is an effective solution for promoting diabetic wound healing. However, ADSCs may experience a reduction in their biological functions when exposed to high glucose levels, which is important to note. Therefore, this study utilized deferoxamine (DFO) to induce a hypoxic microenvironment in mice in order to maintain and promote the effectiveness of ADSCs in treating diabetic wounds. In this study, elevated glucose levels negatively impact ADSCs, but DFO improves viability, secretion, and differentiation. Additionally, ADSCs can also inhibit the polarization of macrophages to M1 by up-regulating HSP70 and inhibiting NF-κB, and promote the polarization of macrophages to the M2 phenotype. Significantly, combining ADSCs with DFO led to a greater enhancement in their ability to promote angiogenesis and regulate macrophage polarization. In the in vivo study, it was observed that compared to the individual use of DFO or ADSCs, their combined use had a significant impact on enhancing the healing of diabetic wounds. These results demonstrated that the application of DFO can effectively reduce the detrimental effects of high glucose on ADSCs, thereby boosting their function in promoting angiogenesis and managing macrophage polarization, and improving the healing of diabetic wounds.