title: Proangiogenic compositions of microvesicles derived from human umbilical cord mesenchymal stem cells.
abstract: OBJECTIVE
  Microvesicles (MVs) derived from mesenchymal stem cells (MSCs) have been shown to promote angiogenesis. This study was aimed to shed a light on the mechanisms by analyzing the angiogenesis-promoting compositions of MSC-MVs. Also we try to figure out the impact of hypoxia on angiogenesis.
  
  
  METHODS
  MVs were isolated from the culture supernatants of MSCs under hypoxia/normoxia and serum-deprivation condition. The morphological features of MVs were revealed by an electron microscope and the origin of the MVs was identified by a bead-bound assay. An antibody array was used to analyze the expression of angiogenic cytokines from MVs and the parent MSCs as well. The major candidate factors were screened and the results were validated by immune blotting.
  
  
  RESULTS
  MSC-MVs were around 80 nm in diameter. They expressed CD29, CD44, and CD73, but not CD31 and CD45. Antibody array showed that both MSCs and MVs expressed many angiogenesis-promoting biomolecules, including interleukin-6 (IL-6), basic fibroblast growth factors (bFGF), and recptor of urokinase-type plasminogen activator (UPAR). MSC-MVs contained angiogenin, vascular endothelial growth factor (VEGF), monocyte chemotactic protein-1 (MCP-1) and the receptor-2 for vascular endothelial growth factor at higher levels than the parent MSCs. Under hypoxic condition most cytokines were expressed in greater quantity than normoxic in MSCs while in MVs there was no significant difference between hypoxic and normoxic conditions except UPAR, Angiogenin, VEGF, IGF, Tie-2/TEK, and IL-6 which were higher in MVs under hypoxic conditions than those in normoxic condition.
  
  
  CONCLUSIONS
  Upon serum-deprivation condition, MSCs could secrete MVs that contain a variety of factors contributing to their angiogenesis-promoting function. And among them, Angiogenin, VEGF, MCP-1, VEGF R2 might be of greater importance than the other cytokines. Also UPAR, Angiogenin, VEGF, IGF, Tie-2/TEK, IL-6 might be responsible for hypoxia-augmented proangiogenic effects of MVs.
authors.affiliation: Division of Cardiovascular Disease, Department of Internal Medicine, Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong, China.
authors.forename: Jianying
authors.initials: J
authors.lastname: Chen
authors.affiliation: Division of Cardiovascular Disease, Department of Internal Medicine, Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong, China.
authors.forename: Zhenjun
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Division of Cardiovascular Disease, Department of Internal Medicine, Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong, China.
authors.forename: Mian Ming
authors.initials: MM
authors.lastname: Hong
authors.affiliation: Division of Cardiovascular Disease, Department of Internal Medicine, Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong, China.
authors.forename: Hongzhe
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Division of Cardiovascular Disease, Department of Internal Medicine, Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong, China.
authors.forename: Can
authors.initials: C
authors.lastname: Chen
authors.affiliation: Division of Cardiovascular Disease, Department of Internal Medicine, Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong, China.
authors.forename: Mengyuan
authors.initials: M
authors.lastname: Xiao
authors.affiliation: Division of Cardiovascular Disease, Department of Internal Medicine, Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong, China.
authors.forename: Junxian
authors.initials: J
authors.lastname: Wang
authors.affiliation: Division of Cardiovascular Disease, Department of Internal Medicine, Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Yao
authors.affiliation: Division of Cardiovascular Disease, Department of Internal Medicine, Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong, China.
authors.forename: Mingchuan
authors.initials: M
authors.lastname: Ba
authors.affiliation: Division of Cardiovascular Disease, Department of Internal Medicine, Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong, China.
authors.forename: Jinghu
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing, China.
authors.forename: Zi-Kuan
authors.initials: ZK
authors.lastname: Guo
authors.affiliation: Division of Cardiovascular Disease, Department of Internal Medicine, Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong, China; Division of Cardiovascular Medicine, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Jixin
authors.initials: J
authors.lastname: Zhong
mesh_terms: D000704:Analysis of Variance; D015153:Blotting, Western; D018932:Chemokine CCL2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D008855:Microscopy, Electron, Scanning; D055806:Microvessels / Q000502:physiology* / Q000648:ultrastructure; D018919:Neovascularization, Physiologic / Q000502:physiology*; D012259:Ribonuclease, Pancreatic / Q000378:metabolism; D014470:Umbilical Cord / Q000166:cytology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; D016207:Cytokines; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C046366:angiogenin; D012259:Ribonuclease, Pancreatic