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

Shao-Chun Wu,Hang-Tsung Liu,Pao-Jen Kuo,Chun-Ying Huang,Chia-Wei Lin,Yi-Chan Wu,Cheng-Shyuan Rau,Chia-Wen Tsai,Lien-Hung Huang,Chia-Jung Wu,Ting-Min Hsieh,Ching-Hua Hsieh

doi:10.3390/ijms22168877

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.

Highlights

Cell-based therapies, such as those comprising adipose-derived stem cells (ADSCs), are considered promising for improving wound healing [1], even in difficult situations such 4.0/).as chronic diabetic wounds [2,3] and irradiated wounds [4,5]
The results revealed that human umbilical vein endothelial cells (HUVECs) treated with ADSCLPS-exo had significantly enhanced cell migration (Figure 5) and tube formation (Figure 6), which manifested as increased total vessel lengths and the total number of junctions detected by Angiotool, compared to those treated with ADSC-exo
This phenomenon is related to the activation of cAMP response element binding protein (CREB), activating protein 1 (AP-1), and nuclear factor-κB (NF-κB) signal transduction pathways and IL-8 production in recipient HUVECs during exosome treatment

Summary

Introduction

Cell-based therapies, such as those comprising adipose-derived stem cells (ADSCs), are considered promising for improving wound healing [1], even in difficult situations such 4.0/).as chronic diabetic wounds [2,3] and irradiated wounds [4,5]. ADSCs secrete a rich secretome to enhance cell differentiation, proliferation, migration, and tissue regeneration in the cellular microenvironment [10,11,12,13]. ADSC-exo has been demonstrated to accelerate cutaneous wound healing by promoting vascularization, tissue regeneration, proliferation, and the re-epithelialization of skin cells [13,15,16,17]. Many clinical studies have demonstrated that exosomes secreted by autologous or allogeneic mesenchymal stem cells (MSCs) and ADSCs can enhance the healing process of chronic wounds by inducing angiogenesis and tissue regeneration [20,21]. Exosomes released from educated MSCs accelerate cutaneous wound healing by promoting angiogenesis [23,24]. In clinical settings, wounds may be infected by various bacteria

Methods

Results

Discussion

Conclusion