Extracellular Vesicles Derived from Hypoxia Treated Human Adipose Stem Cells Increase Proliferation and Angiogenic Differentiation in Human Adipose Stem Cells.

Abstract

Adipose-derived stem cells (ADSCs) are crucial in cell-assisted lipotransfer (CAL). ADSC-derived exosomes could improve the survival of CAL. Almost all relevant research now ignores ADSCs in favor of studying the proangiogenic potential of extracellular vesicles (EVs) on human umbilical vein endothelial cells (HUVECs). Given the significance of ADSCs in CAL, the authors sought to verify that EVs from ADSCs under hypoxia treatment can enhance the angiogenic potential of ADSCs. EVs were harvested from human ADSCs (hADSCs) under normoxia and hypoxia. A Cell Counting Kit-8 (CCK-8) assay was used to measure the proliferation of hADSCs. By examining the expression of CD31, vascular endothelial growth factor receptor 2 and vascular endothelial growth factor, the pro-angiogenic differentiation potential was assessed. Moreover, a tube formation experiment was carried out to evaluate the pro-angiogenic differentiation potential. Hypoxic EVs showed more significant pro-proliferative and pro-angiogenic potential. Angiogenesis was more vigorous in hADSCs treated with hypoxic EVs than in those treated with nomorxic EVs. The hADSCs treated with hypoxic EVs expressed higher angiogenic markers, according to real-time polymerase chain reaction (RT‒PCR) and Western blot analysis, which revealed more angiogenic marker expression in hypoxic EV-treated hADSCs. The same result was demonstrated by tube formation on Matrigel in vitro. Hypoxic EVs significantly increased the proliferation and angiogenic differentiation potential of hADSCs. Hypoxic EV-treated ADSCs may be beneficial to CAL and prevascularized tissue-engineered constructs.