Extracellular Vesicles from Human Adipose-Derived Stem Cells for the Improvement of Angiogenesis and Fat-Grafting Application

Background: The efficacy of autologous fat transplantation is reduced by fat absorption and fibrosis that are closely related to unsatisfactory vascularization. Extracellular vesicles are key components of the cell secretome, which can mirror the functional and molecular characteristics of their parental cells. Growing evidence has revealed that adipose-derived mesenchymal stem cells have the ability to enhance vascularization, which is partly ascribed to extracellular vesicles. The authors evaluated whether adipose-derived mesenchymal stem cell-derived extracellular vesicles improved vascularization of fat grafts and increased their retention rate. Methods: To test the angiogenesis ability of adipose-derived mesenchymal stem cell-derived extracellular vesicles, they were isolated from the supernatant of cultured human adipose-derived mesenchymal stem cells and incubated with human umbilical vein endothelial cells in vitro. Then, the vesicles were co-transplanted with fat into nude mice subcutaneously. Three months after transplantation, the retention rate and inflammatory reaction of the grafts were analyzed by histologic assay. Results: The experimental group could significantly promote migration and tube formation at the concentration of 20 mu g/ml. At 3 months after transplantation, the volume of the experimental group (0.12 +/- 0.03 mm(3)) was larger compared with the blank group (0.05 +/- 0.01 mm(3)). Histology and immunohistology results demonstrated significantly fewer cysts and vacuoles, less fibrosis, and more neovessels in the extracelluar vesicle group. Conclusions: The authors co-transplanted adipose-derived mesenchymal stem cell-derived extracellular vesicles with fat into a nude mouse model and found that the vesicles improved volume retention by enhancing vascularization and regulating the inflammatory response.