Inhibition of Ferroptosis by Adipose Stem Cell-Derived Apoptotic Vesicles Enhances Angiogenesis and Accelerates Diabetic Wound Healing

作者：Jingyi Zhang, Jinxin Kuang, Shengkai Gong, Hanzhe Wang, Feng Ding, Lu Zhao, Lele Shi, Shiyu Liu, Yimin Zhao, Jiani Liu, Geng Dou · 发表于：International Journal of Nanomedicine · 年份：2025 · DOI：10.2147/ijn.s527475 · 被引用次数：7 · 研究领域：Extracellular vesicles in disease、Ferroptosis and cancer prognosis、Immune cells in cancer

Purpose: Impaired angiogenesis is a critical challenge in diabetic wound healing. While apoptotic derivatives of stem cells hold promise for regenerative therapy, their role in modulating angiogenesis within the diabetic wound microenvironment remains underexplored. This study aims to investigate whether adipose stem cell-derived apoptotic vesicles (ASCs-apoVs) promote angiogenesis and accelerate diabetic wound healing by inhibiting endothelial cell ferroptosis. Methods: Diabetic mice model was established by feeding with high-fat diet (HFD) for 3 months followed by full-thickness skin wound preparation. Adipose stem cells (ASCs) isolated from adipose tissue were treated with staurosporine (STS) to induce apoptosis in vitro. Apoptotic vesicles (apoVs) were isolated by differential centrifugation, characterized using TEM, dynamic light scattering (DLS), and Western blot, and applied topically to diabetic wounds. The therapeutic effects of apoVs on wound healing efficiency, vascularization level and endothelial cell ferroptosis were evaluated. Results: vessel density and delayed wound closure. In vitro diabetic endothelial cell models confirmed increased lipid peroxidation and ferroptosis, which compromised the proliferation, migration and tube formation capacities of ECs. ASCs-apoVs, characterized by typical extracellular vesicle (EV) morphology and apoptotic markers, significantly inhibited lipid peroxidation and ferroptosis of ECs, thereby promoting angiogenesis and accelera...