Mscs Apoptotic Vesicles Attenuated Endothelial Cell Ferroptosis For Angiogenesis

Investigating adipose-derived stem cell apoptotic vesicles (ASCs-apoVs) as angiogenic mediators through ferroptosis inhibition for enhanced diabetic wound repair. C57BL/6J mice were fed a high-fat diet (HFD) from six weeks of age for at least 3 months to construct diabetic mouse models. Wound healing model was established by creating a full-thickness circular wound (10 mm diameter) on the dorsal skin of control (Ctrl) or HFD mice. ASCs-ApoVs were isolated and characterized using scanning electron microscopy, dynamic light scattering (DLS) analysis, and Western blotting. The therapeutic effects of ApoVs on healing efficiency and neovascularization were evaluated through H&E staining, Masson’s trichrome staining, and immunofluorescence. Ferroptosis levels in endothelial cells were assessed by measuring cell viability, reactive oxygen species (ROS) levels, and lipid peroxidation. Scratch assays and tube formation assays were performed to validate the therapeutic potential of ASCs-ApoVs in regulating endothelial cell function. HFD-induced diabetes triggered ferroptosis of endothelial cells resulting in impaired vascularization and delayed wound healing. ASCs-ApoVs were successfully isolated and characterized, exhibiting the typical features of extracellular vesicles. ApoVs were found to inhibit ferroptosis in endothelial cells, thereby promoting angiogenesis and accelerating diabetic wound healing. Ferroptosis of endothelial cells is a major contributor to impaired vascularization during diabetic wound healing. ApoVs represent a promising cell-free therapeutic approach to restore endothelial cell function and promote angiogenesis, offering an alternative strategy for diabetic wound management.