Human peripheral blood-derived CD31+ cells have robust angiogenic and vasculogenic properties and are effective for treating ischemic vascular disease.
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.
Kim
Sung-Whan
SW
Division of Cardiology, Department of Medicine, Emory University School of Medicine, 1639 Pierce Drive, Atlanta, GA 30322, USA.
Kim
Hyongbum
H
Cho
Hyun-Jai
HJ
Lee
Jung-Uek
JU
Levit
Rebecca
R
Yoon
Young-sup
YS
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*
D015415:Biomarkers; D019408:Platelet Endothelial Cell Adhesion Molecule-1