Proangiogenic Compositions of Microvesicles Derived from Human Umbilical Cord Mesenchymal Stem Cells

被引：85

作者：

Chen, Jianying ^{[1
]}

Liu, Zhenjun ^{[1
]}

Hong, Mian Ming ^{[1
]}

Zhang, Hongzhe ^{[1
]}

Chen, Can ^{[1
]}

Xiao, Mengyuan ^{[1
]}

Wang, Junxian ^{[1
]}

Yao, Feng ^{[1
]}

Ba, Mingchuan ^{[1
]}

Liu, Jinghu ^{[1
]}

Guo, Zi-Kuan ^{[2
]}

Zhong, Jixin ^{[1
,3
]}

机构：

[1] Affiliated Hosp, Guangdong Med Coll, Dept Internal Med, Div Cardiovasc Dis, Zhanjiang, Guangdong, Peoples R China

[2] Beijing Inst Radiat Med, Dept Expt Hematol, Beijing, Peoples R China

[3] Univ Maryland, Sch Med, Dept Med, Div Cardiovasc Med, Baltimore, MD 21201 USA

来源：

PLOS ONE | 2014年 / 9卷 / 12期

基金：

中国国家自然科学基金;

关键词：

IN-VITRO; MATRIX METALLOPROTEINASES; REPERFUSION INJURY; ANGIOGENESIS; ACTIVATION; MECHANISMS; EXOSOMES; THERAPY; BLOOD; VIVO;

D O I：

10.1371/journal.pone.0115316

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Introduction & 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. Conclusion: 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.

引用

页数：16

共 28 条

[11]

Exosomes reflect the hypoxic status of glioma cells and mediate hypoxia-dependent activation of vascular cells during tumor development [J].