Proangiogenic compositions of microvesicles derived from human umbilical cord mesenchymal stem cells

• Published in: PloS one 2014-12, Vol.9 (12), p.e115316-e115316
• Main Authors: Chen, Jianying, Liu, Zhenjun, Hong, Mian Ming, Zhang, Hongzhe, Chen, Can, Xiao, Mengyuan, Wang, Junxian, Yao, Feng, Ba, Mingchuan, Liu, Jinghu, Guo, Zi-Kuan, Zhong, Jixin
• Format: Article
• Language: English
• Subjects: Analysis; Analysis of Variance; Angiogenesis; Angiogenin; Apoptosis; Biology and Life Sciences; Biomolecules; Blotting, Western; Cardiovascular disease; CD29 antigen; CD44 antigen; CD45 antigen; CD73 antigen; Cell culture; Chemokine CCL2 - metabolism; Cytokines; Cytokines - metabolism; Deprivation; Fibroblast growth factor 2; Fibroblast growth factors; Growth factors; Hospitals; Human subjects; Humans; Hypoxia; Hypoxia - physiopathology; Immunoglobulins; Insulin-like growth factors; Interleukin 6; Internal medicine; Ischemia; Medicine; Medicine and Health Sciences; Mesenchymal stem cells; Mesenchymal Stromal Cells - physiology; Mesenchyme; Microscopy, Electron, Scanning; Microvessels - physiology; Microvessels - ultrastructure; Monocyte chemoattractant protein 1; Neovascularization, Physiologic - physiology; Ribonuclease, Pancreatic - metabolism; Stem cells; U-Plasminogen activator; Umbilical cord; Umbilical Cord - cytology; Urokinase; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - metabolism
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0115316

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. 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. 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. 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.