Journal
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
Volume 56, Issue 7, Pages 593-607Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jacc.2010.01.070
Keywords
CD31; endothelial cells; angiogenesis; vasculogenesis; ischemic hind limb
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Funding
- National Institute of Health [HL079137, HL084471, HL097353]
- Ministry of Education, Science and Technology, Republic of Korea [SC4300]
- Korea Research Foundation, Republic of Korea (MOEHRD)
- Atlanta Clinical Translational Research Institute (ACTSI)-Georgia Tech Emory Collaboration for Regenerative Medicine and Engineering (GTEC)
- National Research Foundation of Korea [12-2008-00-002-00] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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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 wellknown 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. (J Am Coll Cardiol 2010;56:593-607) (C) 2010 by the American College of Cardiology Foundation
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