title: Microvesicles derived from human umbilical cord mesenchymal stem cells stimulated by hypoxia promote angiogenesis both in vitro and in vivo.
abstract: Although mesenchymal stem cells (MSCs) have been increasingly trialed to treat a variety of diseases, the underlying mechanisms remain still elusive. In this study, human umbilical cord (UC)-derived MSCs were stimulated by hypoxia, and the membrane microvesicles (MVs) in the supernatants were collected by ultracentrifugation, observed under an electron microscope, and the origin was identified with the flow cytometric technique. The results showed that upon hypoxic stimulus, MSCs released a large quantity of MVs of ~100 nm in diameter. The MVs were phenotypically similar to the parent MSCs, except that the majority of them were negative for the receptor of platelet-derived growth factor. DiI-labeling assay revealed that MSC-MVs could be internalized into human UC endothelial cells (UC-ECs) within 8 h after they were added into the culture medium. Carboxyfluorescein succinimidyl ester-labeling technique and MTT test showed that MSC-MVs promoted the proliferation of UC-ECs in a dose-dependent manner. Further, MVs could enhance in vitro capillary network formation of UC-ECs in a Matrigel matrix. In a rat hindlimb ischemia model, both MSCs and MSC-MVs were shown to improve significantly the blood flow recovery compared with the control medium (P<0.0001), as assessed by laser Doppler imaging analysis. These data indicate that MV releasing is one of the major mechanisms underlying the effectiveness of MSC therapy by promoting angiogenesis.
authors: Department of Cardiology Surgery, General Hospital of Air Force, Beijing, China.
authors: Hong-Chao
authors: HC
authors: Zhang
authors: Xin-Bin
authors: XB
authors: Liu
authors: Shu
authors: S
authors: Huang
authors: Xiao-Yun
authors: XY
authors: Bi
authors: Heng-Xiang
authors: HX
authors: Wang
authors: Li-Xian
authors: LX
authors: Xie
authors: Yong-Qi
authors: YQ
authors: Wang
authors: Xiao-Fang
authors: XF
authors: Cao
authors: Jun
authors: J
authors: Lv
authors: Feng-Jun
authors: FJ
authors: Xiao
authors: Yang
authors: Y
authors: Yang
authors: Zi-Kuan
authors: ZK
authors: Guo
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D015687:Cell Hypoxia; D021961:Cell Membrane Structures / Q000502:physiology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D005434:Flow Cytometry; D005452:Fluoresceins; D006614:Hindlimb / Q000098:blood supply*; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D007511:Ischemia; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D018919:Neovascularization, Physiologic / Q000502:physiology*; D051381:Rats; D017479:Receptors, Platelet-Derived Growth Factor; D013388:Succinimides; D014470:Umbilical Cord / Q000166:cytology
chemical_list: C087165:5-(6)-carboxyfluorescein diacetate succinimidyl ester; D005452:Fluoresceins; D013388:Succinimides; D017479:Receptors, Platelet-Derived Growth Factor