title: Surface Phosphatidylserine Is Responsible for the Internalization on Microvesicles Derived from Hypoxia-Induced Human Bone Marrow Mesenchymal Stem Cells into Human Endothelial Cells.
abstract: BACKGROUND
  Previous data have proven that microvesicles derived from hypoxia-induced mesenchymal stem cells (MSC-MVs) can be internalized into endothelial cells, enhancing their proliferation and vessel structure formation and promoting in vivo angiogenesis. However, there is a paucity of information about how the MSC-MVs are up-taken by endothelial cells.
  
  
  METHODS
  MVs were prepared from the supernatants of human bone marrow MSCs that had been exposed to a hypoxic and/or serum-deprivation condition. The incorporation of hypoxia-induced MSC-MVs into human umbilical cord endothelial cells (HUVECs) was observed by flow cytometry and confocal microscopy in the presence or absence of recombinant human Annexin-V (Anx-V) and antibodies against human CD29 and CD44. Further, small interfering RNA (siRNA) targeted at Anx-V and PSR was delivered into HUVECs, or HUVECs were treated with a monoclonal antibody against phosphatidylserine receptor (PSR) and the cellular internalization of MVs was re-assessed.
  
  
  RESULTS
  The addition of exogenous Anx-V could inhibit the uptake of MVs isolated from hypoxia-induced stem cells by HUVECs in a dose- and time-dependent manner, while the anti-CD29 and CD44 antibodies had no effect on the internalization process. The suppression was neither observed in Anx-V siRNA-transfected HUVECs, however, addition of anti-PSR antibody and PSR siRNA-transfected HUVECs greatly blocked the incorporation of MVs isolated from hypoxia-induced stem cells into HUVECs.
  
  
  CONCLUSIONS
  PS on the MVs isolated from hypoxia-induced stem cells is the critical molecule in the uptake by HUVECs.
authors.affiliation: Department of Cardiology Surgery, General Hospital of Air Force, Beijing, China.
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Wei
authors.affiliation: Department of Cardiology Surgery, General Hospital of Air Force, Beijing, China.
authors.forename: Chaozhong
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Hematology, General Hospital of Air Force, Beijing, China.
authors.forename: Hengxiang
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing, China.
authors.forename: Lisheng
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing, China.
authors.forename: Fengjun
authors.initials: F
authors.lastname: Xiao
authors.affiliation: Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing, China.
authors.forename: Zikuan
authors.initials: Z
authors.lastname: Guo
authors.affiliation: Department of Cardiology Surgery, General Hospital of Air Force, Beijing, China.
authors.forename: Hongchao
authors.initials: H
authors.lastname: Zhang
mesh_terms: D017304:Annexin A5 / Q000235:genetics; D001854:Bone Marrow Cells / Q000378:metabolism*; D015687:Cell Hypoxia; D004705:Endocytosis / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D010718:Phosphatidylserines / Q000502:physiology*; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: D017304:Annexin A5; D010718:Phosphatidylserines; D034741:RNA, Small Interfering