Small Extracellular Vesicles From Human Adipose-derived Stem Cells: A Potential Promoter of Keeping Fat Graft Survival

Abstract Background: Small extracellular vesicles (sEVs) with genetic information secreted by cells play a crucial role in the cellular microenvironment. In this study, our purpose is to explore the characteristics of the small extracellular vesicles of human adipose-derived stem cells (hADSC-sEVs) and studied the role of hADSC-sEVs in improving the survival rate of grafted fat.Methods: In the present study, we used the transmission electron microscopy, nano-tracking analysis, nanoflow surface protein analysis, zeta potential value to identify sEVs. SEVs' trajectory was traced dynamically to verify whether hADSC-sEVs can be internalized into human umbilical vein endothelial cells (HUVECs) in vitro. The angiogenic property of hADSC-sEVs was observed by measuring the volume, weight and histological analysis of the grafted fats in nude mice modles. Results: Our research showed that the extracellular vesicles were sEVs with double-layer membrane structure and the diameter of which is within 30-150nm. hADSC-sEVs exert biological influence mainly through internalization into cells. Compared with the control group, the hADSC-sEVs group had a significantly higher survival rate of grafted fat, morphological integrity and a lower degree of inflammation and fibrosis. And immunohistochemistry showed that hADSC-sEVs significantly increased the neovascularisation and the expression of CD34, VEGFR2 and KI-67 in the graft tissue. Conclusions: As a potential nanomaterial, hADSC-sEVs has been explored in the field of cell-free application of stem cell technology. hADSC-sEVs promoted the survival of grafted fats by promoting the formation of new blood vessels, which is another promising progress in the field of regenerative medicine. We believe that hADSC-sEVs will have a broad application prospect in the field of regenerative medicine in the future.