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

Abstract

Exosomes secreted by adipose-derived stem cells (ADSCs) enhance angiogenesis and wound healing. However, in clinical settings, wounds may be infected by various bacteria or pathogens. We investigated whether human ADSCs stimulated with lipopolysaccharide (LPS) secrete exosomes (ADSC-LPS-exo) that augment the angiogenesis of human umbilical vein endothelial cells (HUVECs). ExoQuick-TC exosome precipitation solution was used to purify exosomes from human ADSC culture media in the presence or absence of 1 µg/mL LPS treatment for 24 h. The uptake of ADSC-LPS-exo significantly induced the activation of cAMP response element binding protein (CREB), activating protein 1 (AP-1), and nuclear factor-κB (NF-κB) signaling pathways and increased the migration of and tube formation in HUVECs. RNA interference with CREB, AP-1, or NF-κB1 significantly reduced the migration of and tube formation in HUVECs treated with ADSC-LPS-exo. An experiment with an antibody array for 25 angiogenesis-related proteins revealed that only interleukin-8 expression was significantly upregulated in HUVECs treated with ADSC-LPS-exo. In addition, proteomic analysis revealed that eukaryotic translation initiation factor 4E, amyloid beta A4 protein, integrin beta-1, and ras-related C3 botulinum toxin substrate 1 may be potential candidates involved in ADSC-LPS-exo-mediated enhanced angiogenesis.

Extracellular vesicle-loaded hydrogels for tissue repair and regeneration

“…The role of hypoxic ADSC-EVs in cartilage regeneration has also been evaluated; upregulation of chondrocyte-related gene expression in hypoxic ADSC-EVs was found to induce more cartilage matrix and proteoglycan production, and this study is expected to play an important role in cartilage tissue engineering [ 65 ]. Hypoxia is only one of the more classic pretreatment strategies, but there are many others, such as the addition of lipopolysaccharides [ 66 ], hydrogen peroxide [ 66 ], hydrogen peroxide [ 67 ], atorvastatin [ 68 ], and pioglitazone [ 69 ]. EV activity can also be enhanced by engineering or genetic strategies, including surface modifications, genetic modification, and epigenetic reprogramming [ 41 , 70 , 71 ].…”

Angiogenic activity of mitochondria; beyond the sole bioenergetic organelle

“…Along with these changes, the promotion of SIRT3 can reduce mitochondrial damage by the stimulation of SOD2 in EPCs (Zhang, Bai, et al, 2022). LPS‐exposed stem cells can secret exosomes with cAMP response element‐binding protein, AP‐1, and NF‐κB leading to migration, proliferation, and angiogenesis properties of HUVECs (Wu et al, 2021). These data indicated that exosomes can, directly and indirectly, regulate the angiogenic potential of ECs under physiological and pathological conditions.…”

Current Status of Mesenchymal Stem/Stromal Cells for Treatment of Neurological Diseases

“…Priming of MSCs with toll-like receptor III agonist poly(I:C) upregulated EV proteins related to immune response, among other processes (Pierce and Kurata, 2021 ). Exosomes derived from human AT-MSCs stimulated by LPS increased in angiogenic potential (Wu et al, 2021 ). Preconditioning of MSCs with IFN-γ induced release of Evs containing annexin-1, lactotransferrin, and aminopeptidase N (Takeuchi et al, 2021 ).…”