Abstract
Extracellular vesicles (EVs) derived from human adipose-derived stem cells (hADSCs) possess the proangiogenic potential for ischaemic diseases. Thus, our study aimed to evaluate the therapeutic effects of hADSC-EVs on fat grafting and explore the mechanism of hADSC-EVs promoting angiogenesis. The EVs released by hADSCs incubated under normal or hypoxic conditions were employed to supplement fat grafting in a nude mouse model. The proliferation, migration, tube formation and vascular endothelial growth factor (VEGF) secretion of vascular endothelial cells co-cultured with two kinds of hADSC-EVs were analysed. MicroRNA sequencing was performed to reveal the species and content of microRNAs in hADSC-EVs, the key microRNAs were blocked, and their effect in promoting angiogenesis was detected via above protocols as a reverse proof. The results demonstrate that hADSC-EVs could improve the survival of fat grafts by promoting exogenous angiogenesis and enhance the proliferation, migration, tube formation and VEGF secretion of vascular endothelial cells. In addition, the pro-angiogenic effect of hADSC-EVs in vivo and vitro could be enhanced by hypoxic pre-treatment. We found that the let-7 family, a kind of hypoxic-related microRNA, is enriched in hypoxic hADSC-EVs that contribute to angiogenesis via the let-7/argonaute 1 (AGO1)/VEGF signalling pathway.
Highlights
Extracellular vesicles (EVs) derived from human adipose-derived stem cells possess the proangiogenic potential for ischaemic diseases
This study aimed to demonstrate the effect of hypoxia-induced extracellular vesicles derived from human adipose-derived stem cells in promoting graft survival in a mouse model and the role of key microRNAs in promoting angiogenesis under hypoxic conditions
The EVs extracted from the supernatant of human adipose-derived stem cells (hADSCs) cultured under hypoxic or normal conditions or LIN28B transfection exhibited few differences by the detection of transmission electron microscopy (TEM), NanoSight and western blot
Summary
Extracellular vesicles (EVs) derived from human adipose-derived stem cells (hADSCs) possess the proangiogenic potential for ischaemic diseases. The results demonstrate that hADSC-EVs could improve the survival of fat grafts by promoting exogenous angiogenesis and enhance the proliferation, migration, tube formation and VEGF secretion of vascular endothelial cells. With the progress on the research of the biological functions of MSCs, for fat grafting, the paracrine effect of adipose-derived stem cells (ADSCs) play important roles in angiogenesis and tissue regeneration[8]. Studies in recent years have proposed that[9,10,11] stem cells may have stronger paracrine functions under stress conditions, such as ischaemia and hypoxia, to promote the repair of ischaemic and hypoxic tissues. This study aimed to demonstrate the effect of hypoxia-induced extracellular vesicles derived from human adipose-derived stem cells (hADSC-EVs) in promoting graft survival in a mouse model and the role of key microRNAs in promoting angiogenesis under hypoxic conditions
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