Exosomes from hypoxia-treated human adipose-derived mesenchymal stem cells enhance angiogenesis through VEGF/VEGF-R. 2019

Yudi Han, and Jing Ren, and Yun Bai, and Xuetao Pei, and Yan Han
Department of Plastic and Reconstructive Surgery, First Medical Center of PLA General Hospital, Beijing 100853, P.R. China; Department of Burn and Plastic Surgery, Seventh Medical Center of PLA General Hospital, Beijing 100700, P.R. China; Nankai University School of Medicine, Tianjin 300000, P.R. China. Electronic address: hanyudi_301@foxmail.com.

We previously reported that co-transplantation of exosomes from hypoxia-preconditioned adipose mesenchymal stem cells (ADSCs) improves the neoangiogenesis and survival of the grafted tissue. This study aimed to investigate the molecular mechanism of this protective effect. Exosomes were collected from normoxia-treated (nADSC-Exo) or hypoxia--treated (hypADSC-Exo) human ADSCs, and their pro-angiogenic capacity was evaluated in human umbilical vein endothelial cells (HUVECs) and a nude mouse model of subcutaneous fat grafting. Protein array was used to compare the exosome-derived proteins between nADSC-Exo and hypADSC-Exo. Compared with the nADSC-Exo group and untreated control, hypADSC-Exo treatment significantly promoted proliferation, migration and tube-formation capability of HUVECs. Protein array revealed that the levels of vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), fibroblast growth factor (FGF) and their receptors (VEGF-R2, VEGF-R3), and monocyte chemoattractant protein 2 (MCP-2), monocyte chemoattractant protein 4 (MCP-4) were significantly higher in the hypADSC-Exo than in the nADSC-Exo. In the nude mice model of fat grafting, immunofluorescence of CD31 showed that hypADSC-Exo dramatically improved neovascularization around the graft. Furthermore, compared with nADSC-Exo and control groups, cotransplantation of hypADSC-Exo significantly increased the protein expression of EGF, FGF, VEGF/VEGF-R, angiopoietin-1(Ang-1) and tyrosine kinase with immunoglobulin-like and EGF-like domains 1(Tie-1, an angiopoietin receptor) in the grafted tissue at 30 days after transplantation. Immunohistochemical analysis demonstrated that hypADSC-Exo treatment significantly increased VEGF-R expression in the grafted tissue. Exosomes from hypoxia-treated human ADSCs possess a higher capacity to enhance angiogenesis in fat grafting, at least partially, via regulating VEGF/VEGF-R signaling.

UI MeSH Term Description Entries
D008807 Mice, Inbred BALB C An inbred strain of mouse that is widely used in IMMUNOLOGY studies and cancer research. BALB C Mice, Inbred,BALB C Mouse, Inbred,Inbred BALB C Mice,Inbred BALB C Mouse,Mice, BALB C,Mouse, BALB C,Mouse, Inbred BALB C,BALB C Mice,BALB C Mouse
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000273 Adipose Tissue Specialized connective tissue composed of fat cells (ADIPOCYTES). It is the site of stored FATS, usually in the form of TRIGLYCERIDES. In mammals, there are two types of adipose tissue, the WHITE FAT and the BROWN FAT. Their relative distributions vary in different species with most adipose tissue being white. Fatty Tissue,Body Fat,Fat Pad,Fat Pads,Pad, Fat,Pads, Fat,Tissue, Adipose,Tissue, Fatty
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D015398 Signal Transduction The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal
D015687 Cell Hypoxia A condition of decreased oxygen content at the cellular level. Anoxia, Cellular,Cell Anoxia,Hypoxia, Cellular,Anoxia, Cell,Anoxias, Cell,Anoxias, Cellular,Cell Anoxias,Cell Hypoxias,Cellular Anoxia,Cellular Anoxias,Cellular Hypoxia,Cellular Hypoxias,Hypoxia, Cell,Hypoxias, Cell,Hypoxias, Cellular
D042461 Vascular Endothelial Growth Factor A The original member of the family of endothelial cell growth factors referred to as VASCULAR ENDOTHELIAL GROWTH FACTORS. Vascular endothelial growth factor-A was originally isolated from tumor cells and referred to as "tumor angiogenesis factor" and "vascular permeability factor". Although expressed at high levels in certain tumor-derived cells it is produced by a wide variety of cell types. In addition to stimulating vascular growth and vascular permeability it may play a role in stimulating VASODILATION via NITRIC OXIDE-dependent pathways. Alternative splicing of the mRNA for vascular endothelial growth factor A results in several isoforms of the protein being produced. Vascular Endothelial Growth Factor,Vascular Endothelial Growth Factor-A,GD-VEGF,Glioma-Derived Vascular Endothelial Cell Growth Factor,VEGF,VEGF-A,Vascular Permeability Factor,Vasculotropin,Glioma Derived Vascular Endothelial Cell Growth Factor,Permeability Factor, Vascular
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D055354 Exosomes A type of extracellular vesicle, containing RNA and proteins, that is secreted into the extracellular space by EXOCYTOSIS when MULTIVESICULAR BODIES fuse with the PLASMA MEMBRANE.

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