Author + information
- Received August 20, 2009
- Revision received January 4, 2010
- Accepted January 11, 2010
- Published online August 10, 2010.
- Sung-Whan Kim, PhD*,
- Hyongbum Kim, MD, PhD*,
- Hyun-Jai Cho, MD, PhD†,
- Jung-Uek Lee, MS‡,
- Rebecca Levit, MD* and
- Young-sup Yoon, MD, PhD*,* ()
- ↵*Reprint requests and correspondence:
Dr. Young-sup Yoon, Division of Cardiology, Department of Medicine, Emory University School of Medicine, 1639 Pierce Drive, WMRB 3309, Atlanta, Georgia 30322
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.
Supported in part by National Institute of Healthgrants (HL079137, HL084471, HL097353); a research grant (SC4300) from Stem Cell Research Center of the 21st Century Frontier Research Programfunded by the Ministry of Education, Science and Technology, Republic of Korea; an overseas post-doctoral fellowship grant from the Korea Research Foundation, Republic of Korea (MOEHRD, to Dr. S.-W. Kim); and an Atlanta Clinical Translational Research Institute(ACTSI)–Georgia Tech Emory Collaboration for Regenerative Medicine and Engineering (GTEC) pilot grant. The authors have reported that they have no relationships to disclose.
- Received August 20, 2009.
- Revision received January 4, 2010.
- Accepted January 11, 2010.
- American College of Cardiology Foundation