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• W2995529441 endingPage "e2588" @default.
• W2995529441 startingPage "e2588" @default.
• W2995529441 abstract "Extracellular vesicles (EVs) secreted from adipose-derived mesenchymal stem cells (ADSCs) (ADSC-EVs) improve flap survival after ischemia-reperfusion injury. Exposure of parent ADSCs to oxidative stress has been shown to enhance this effect, but mechanisms are unclear. We aimed to determine whether angiogenesis-promoting protein and microRNA (miRNA) content is altered in EVs after preconditioning with hydrogen peroxide (H2O2 ADSC-EVs) and whether H2O2 ADSC-EVs can increase viability of random pattern skin flaps.EVs secreted by human ADSCs were isolated after culture in EV-depleted medium ± H2O2. Nanoparticle tracking analysis determined size and concentration of purified EVs. Mass spectrometry and small RNA next-generation sequencing were performed to compare proteomic and miRNA profiles. ADSC-EVs, H2O2 ADSC-EVs, or vehicle were injected into random pattern skin flaps of BALB/c mice (4-5 mice per group). Viable and necrotic areas were measured on day 7, and tissues underwent histologic analysis.Angiogenic and antimicrobial protein content of EVs was altered with H2O2 preconditioning. Functional enrichment analysis identified constitutive photomorphogenesis 9 signalosome (known to direct vascular endothelial growth factor production) as the major enriched Gene Ontology term unique to H2O2 ADSC-EVs. Two miRNAs were increased, and 12 (including 10 antiangiogenic miRNAs) were reduced in H2O2 ADSC-EVs. Enhanced viability (P < 0.05) of flaps treated with H2O2 ADSC-EVs compared with vehicle corresponded to increased capillary density in the H2O2 group (P < 0.001).Altered protein and miRNA content in ADSC-EVs after H2O2 pretreatment likely contributes to enhanced therapeutic effects on flap survival observed in preclinical models." @default.
• W2995529441 created "2019-12-26" @default.
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• W2995529441 date "2019-12-01" @default.
• W2995529441 modified "2023-10-18" @default.
• W2995529441 title "Oxidative Stress Alters Angiogenic and Antimicrobial Content of Extracellular Vesicles and Improves Flap Survival" @default.
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• W2995529441 doi "https://doi.org/10.1097/gox.0000000000002588" @default.
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