Oxidative Stress Alters Angiogenic and Antimicrobial Content of Extracellular Vesicles and Improves Flap Survival

Plastic and Reconstructive Surgery. Global Open
John S MayoLisa M Pierce

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 prod...Continue Reading

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Citations

Apr 28, 2021·Stem Cell Reviews and Reports·Maria Luz Alonso-AlonsoYolanda Diebold
May 10, 2021·Free Radical Biology & Medicine·Gabriel Palermo RuizMarcelo A Mori
Aug 24, 2021·Advanced Therapeutics·Stephanie M KronstadtSteven M Jay

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Methods Mentioned

BETA
affinity purification
protein assay
Assay
RNA-seq
biopsy

Software Mentioned

TargetScan
SigmaPlot
Scaffold Proteome
DAVID
Functional Annotation Clustering Tool in the Database for Anno...
ExoMS
DESeq
Mascot
ImageJ

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