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

Sung Whan Kim, Hyongbum Kim, Hyun Jai Cho, Jung Uek Lee, Rebecca Levit, Young Sup Yoon

Research output: Contribution to journalArticle

83 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)593-607
Number of pages15
JournalJournal of the American College of Cardiology
Volume56
Issue number7
DOIs
Publication statusPublished - 2010 Aug 10

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Vascular Diseases
Ischemia
Extremities
Therapeutic Uses
Reverse Transcriptase Polymerase Chain Reaction
Real-Time Polymerase Chain Reaction
Blood Cells
Endothelial Cells
Cell Transplantation
Transcriptome
Bone Marrow Cells
Blood Vessels
Cardiovascular Diseases
Perfusion
Cytokines
Phenotype
Gene Expression

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

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title = "Human peripheral blood-derived CD31+ cells have robust angiogenic and vasculogenic properties and are effective for treating ischemic vascular disease",
abstract = "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.",
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Human peripheral blood-derived CD31+ cells have robust angiogenic and vasculogenic properties and are effective for treating ischemic vascular disease. / Kim, Sung Whan; Kim, Hyongbum; Cho, Hyun Jai; Lee, Jung Uek; Levit, Rebecca; Yoon, Young Sup.

In: Journal of the American College of Cardiology, Vol. 56, No. 7, 10.08.2010, p. 593-607.

Research output: Contribution to journalArticle

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AU - Kim, Sung Whan

AU - Kim, Hyongbum

AU - Cho, Hyun Jai

AU - Lee, Jung Uek

AU - Levit, Rebecca

AU - Yoon, Young Sup

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