Comparison of Proangiogenic Effects of Adipose-Derived Stem Cells and Foreskin Fibroblast Exosomes on Artificial Dermis Prefabricated Flaps

Abstract

Large prefabricated flaps often suffer from necrosis or poor healing due to a lack of new blood vessels and related factors that promote angiogenesis. The innovative use of adipose-derived stem cell exosomes (ADSC-Exo) resolves the problem of vascularization of prefabricated flaps. We analyzed the differential microRNA (miRNA) expression in ADSC-Exo using nextgeneration sequencing (NGS) technology to explore their potential mechanisms in promoting vascularization. We observed that ADSC-Exo could significantly promote the vascularization of artificial dermis prefabricated flaps compared with human foreskin fibroblast exosomes. NGS indicated that there were some differentially expressed miRNAs in both exosomes. Bioinformatics analysis suggested that significantly upregulated hsa-miR-760 and significantly downregulated hsa-miR-423-3p in ADSC-Exo could regulate the expression of the ITGA5 and HDAC5 genes, respectively, to promote the vascularization of skin flaps. In summary, ADSC-Exo can promote skin-flap vascularization, and thereby resolve the problem of insufficient neovascularization of artificial dermis prefabricated flaps, thus expanding the application of prefabricated skin-flap transplantation.

Adipose stem cells-released extracellular vesicles as a next-generation cargo delivery vehicles: a survey of minimal information implementation, mass production and functional modification

“…Two studies found that ASCs EVs could inhibit the proliferation/migration, and promote the apoptosis of keloid/hypertrophic scar fibroblasts via the regulation of miR-192-5p/IL-17RA/Smad axis [ 23 ] or inhibiting TGF-β1/Smad pathway [ 174 ]. Another two studies reported the essential roles of ASCs EVs in promoting the vascularization of skin flaps [ 163 , 176 ], and one study found that ASCs EVs were comparable to parent ASCs in the inhibition of alloimmune response for vascularized composite allotransplantation [ 13 ]. Recently, ASCs EVs have been investigated in the antiaging of photoaged skin by increasing the mRNA expression of type I collagen, corresponding to the antiaging properties of parent ASCs [ 36 ].…”

Increased Angiogenesis by Exosomes Secreted by Adipose-Derived Stem Cells upon Lipopolysaccharide Stimulation

“…In addition, Western blot analyses of each protein or phosphorylated protein with investigation of the function of these proteins on endothelial cells is necessary to confirm the conclusions. Moreover, the effect on angiogenesis by exosomes secreted from ADSCs upon LPS stimulation may rely on factors other than the protein cargo inside exosomes, such as microRNAs [80,81] or lncRNAs [82], which are known to mediate the function of ADSCs on angiogenesis, and should be considered accordingly. Furthermore, LPS, the stimulator used in this study, is only one of a common bacterial toxin component in infectious wounds.…”

Human adipose-derived stem cells promote seawater-immersed wound healing via proangiogenic effects

“…Unfortunately, growth factor therapy is not currently considered an effective treatment based on preclinical and clinical studies [ 39 ]. Exosomes types of membranous vesicles with a diameter of approximately 30–100 nm that are released from cells into the ECM [ 40 ]. Stem cell exosomes can carry a variety of growth factors and noncoding RNAs, which serve as a medium for cell-to-cell communication and target the biological functions of cells [ 41 , 42 ].…”