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

• Published in: International journal of molecular sciences Vol. 22; no. 16; p. 8877
• Main Authors: Wu, Shao-Chun, Kuo, Pao-Jen, Rau, Cheng-Shyuan, Huang, Lien-Hung, Lin, Chia-Wei, Wu, Yi-Chan, Wu, Chia-Jung, Tsai, Chia-Wen, Hsieh, Ting-Min, Liu, Hang-Tsung, Huang, Chun-Ying, Hsieh, Ching-Hua
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 18.08.2021; MDPI
• Subjects: Angiogenesis; Binding sites; Cell adhesion & migration; Cell Movement; Cell Proliferation; Cells, Cultured; Diabetes; Exosomes - physiology; Genes; Human Umbilical Vein Endothelial Cells - cytology; Human Umbilical Vein Endothelial Cells - drug effects; Human Umbilical Vein Endothelial Cells - physiology; Humans; Infections; Lipopolysaccharides - pharmacology; Mesenchymal Stem Cells - cytology; Mesenchymal Stem Cells - drug effects; Mesenchymal Stem Cells - physiology; Neovascularization, Physiologic; Neutrophils; Proteins; Signal Transduction; Stem cells; Tissue engineering; Vascular endothelial growth factor; Wound healing; adipose-derived stem cells; nuclear factor-κB; angiogenesis; endothelial cell; activating protein 1; interleukin-8; lipopolysaccharide; exosome; cAMP response element binding protein; proteomic analysis
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms22168877

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.