title: Human peripheral blood-derived CD31+ cells have robust angiogenic and vasculogenic properties and are effective for treating ischemic vascular disease.
abstract: OBJECTIVE
  This study aimed to determine if CD31 is a novel marker of a circulating angio-vasculogenic cell population and to establish the cells' therapeutic effects on experimental ischemia.
  
  
  BACKGROUND
  Emerging evidence suggested that therapeutic mechanisms underlying various bone marrow-derived cells are due to paracrine effects. Furthermore, the vasculogenic potential of these cells is under debate. CD31 is a well-known marker for endothelial cells but is also expressed in a fraction of peripheral blood (PB) mononuclear cells.
  
  
  METHODS
  CD31(+) cells were isolated from human PB by magnetic-activated cell sorting. The gene expression profile was examined by deoxyribonucleic acid microarray and real-time reverse transcriptase polymerase chain reaction. Various in vitro endothelial differentiation or vasculogenic assays were conducted. Finally, cells were directly implanted into a mouse hind limb ischemia model to test angiogenic-vasculogenic and therapeutic effects.
  
  
  RESULTS
  Fluorescent-activated cell sorter analysis revealed that PB-CD31(+) cells exhibited endothelial and hematopoietic stem/progenitor markers. CD31(+) cells had higher levels of expression of proangiogenic genes on microarray and real-time reverse transcriptase polymerase chain reaction and generated higher numbers of endothelial progenitor cells than CD31(-) cells did. CD31(+) cells spontaneously formed vascular tubelike structures and exhibited an endothelial cell phenotype in vitro. In a hind limb ischemia model, CD31(+) cell transplantation augmented blood perfusion and prevented limb loss. Both angiogenic cytokines and capillary density were increased, suggesting CD31(+) cells augmented neovascularization.
  
  
  CONCLUSIONS
  CD31 is a novel marker that designates circulating angiogenic and vasculogenic cells. These cells are easily isolated from human PB and thus are a novel candidate for treatment of ischemic cardiovascular disease.
authors.affiliation: Division of Cardiology, Department of Medicine, Emory University School of Medicine, 1639 Pierce Drive, Atlanta, GA 30322, USA.
authors.forename: Sung-Whan
authors.initials: SW
authors.lastname: Kim
authors.forename: Hyongbum
authors.initials: H
authors.lastname: Kim
authors.forename: Hyun-Jai
authors.initials: HJ
authors.lastname: Cho
authors.forename: Jung-Uek
authors.initials: JU
authors.lastname: Lee
authors.forename: Rebecca
authors.initials: R
authors.lastname: Levit
authors.forename: Young-sup
authors.initials: YS
authors.lastname: Yoon
mesh_terms: D000818:Animals; D015415:Biomarkers; D002318:Cardiovascular Diseases / Q000628:therapy; D004195:Disease Models, Animal; D005121:Extremities / Q000098:blood supply*; D006801:Humans; D007511:Ischemia / Q000628:therapy*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D051379:Mice; D018919:Neovascularization, Physiologic; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000097:blood*
chemical_list: D015415:Biomarkers; D019408:Platelet Endothelial Cell Adhesion Molecule-1