Human peripheral blood-derived CD31+ cells have robust angiogenic and vasculogenic properties and are effective for treating ischemic vascular disease

J Am Coll Cardiol. 2010 Aug 10;56(7):593-607. doi: 10.1016/j.jacc.2010.01.070.


Objectives: 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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers
  • Cardiovascular Diseases / therapy
  • Disease Models, Animal
  • Extremities / blood supply*
  • Humans
  • Ischemia / therapy*
  • Leukocytes, Mononuclear / immunology
  • Mice
  • Neovascularization, Physiologic
  • Platelet Endothelial Cell Adhesion Molecule-1 / blood*


  • Biomarkers
  • Platelet Endothelial Cell Adhesion Molecule-1