Abstract
BackgroundSmall 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 mesenchymal stromal cells (hADMSC-sEVs) and studied the role of hADMSC-sEVs in improving the survival rate of grafted fat.MethodsIn the present study, we used the transmission electron microscopy, nano-tracking analysis, nanoflow surface protein analysis, and zeta potential value to identify sEVs. SEVs’ trajectory was traced dynamically to verify whether hADMSC-sEVs can be internalized into human umbilical vein endothelial cells (HUVECs) in vitro at different times. The angiogenic property of hADMSC-sEVs was observed by measuring the volume, weight, and histological analysis of the grafted fats in nude mouse models.ResultsOur research showed that the hADMSC-sEVs were sEVs with double-layer membrane structure and the diameter of which is within 30–150 nm. hADMSC-sEVs exert biological influence mainly through internalization into cells. Compared with the control group, the hADMSC-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 hADMSC-sEVs significantly increased the neovascularisation and the expression of CD34, VEGFR2, and Ki-67 in the graft tissue.ConclusionsAs a potential nanomaterial, hADMSC-sEVs have been explored in the field of cell-free application of stem cell technology. hADMSC-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 hADMSC-sEVs will have a broad application prospect in the field of regenerative medicine in the future.
Highlights
Small extracellular vesicles with genetic information secreted by cells play a crucial role in the cellular microenvironment
To determine the mesenchymal phenotype of hADMSCs, we investigated the purified hADMSCs by using flow cytometry analysis
98% of hADMSCs were positive for CD29 and CD90, but negative for CD31 and CD45 (Fig. 1d)
Summary
Small extracellular vesicles (sEVs) with genetic information secreted by cells play a crucial role in the cellular microenvironment. Our purpose is to explore the characteristics of the small extracellular vesicles of human adipose-derived mesenchymal stromal cells (hADMSC-sEVs) and studied the role of hADMSC-sEVs in improving the survival rate of grafted fat. Small extracellular vesicles (sEVs) are 30–150 nm membranous vesicles actively released by cells [1], containing various kinds of molecules—proteins, mRNA, miRNA, lipids—that are actively being studied as potential biomarkers and play essential roles in intercellular communication [2]. Co-transplantation of autologous adipose tissue with hADMSCs or stromal vascular fraction (SVF), known as cell-assisted lipotransfer (CAL) technique [12], can enhance the survival rates by stimulating angiogenesis through a paracrine effect [13]. Based on the access to previous researches, we hypothesized that hADMSC-sEVs could be a kind of biomaterial applying in promoting vessel reconstruction after transplantation, with satisfactory biocompatibility and retention
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