CD31+ cells represent highly angiogenic and vasculogenic cells in bone marrow: novel role of nonendothelial CD31+ cells in neovascularization and their therapeutic effects on ischemic vascular disease.
BACKGROUND
Bone marrow (BM) cells play an important role in physiological and therapeutic neovascularization. However, it remains unclear whether any specific uncultured BM cell populations have higher angiogenic and vasculogenic activities. Moreover, there has been controversy regarding the vasculogenic ability of BM cells.


OBJECTIVE
Preliminary flow cytometric analysis showed that CD31, traditionally a marker for endothelial cells, is expressed in certain nonendothelial BM mononuclear cells in both human and mouse. Based on the conserved CD31 expression in the axis of hematopoietic stem/progenitor cells (HSC/HPCs) to endothelial cells, we further sought to determine the comprehensive vasculogenic and angiogenic characteristics of human and mouse BM-derived CD31(+) cells.


RESULTS
Flow cytometric analysis demonstrated that all CD31(+) cells derived from BM were CD45(+) and expressed markers for both HSC/HPCs and endothelial cells. Comprehensive gene expression analyses revealed that BM-CD31(+) cells expressed higher levels of angiogenic genes than CD31(-) cells. Endothelial progenitor cells, as well as HSC/HPCs, were almost exclusively confined to the CD31(+) cell fraction, and culture of CD31(+) cells under defined conditions gave rise to endothelial cells. Finally, injection of CD31(+) cells into ischemic hindlimb repaired ischemia, increased expression of angiogenic and chemoattractive factors, and, in part, directly contributed to vasculogenesis, as demonstrated by both 3D confocal microscopy and flow cytometry.


CONCLUSIONS
These data indicate that BM-CD31(+) cells represent highly angiogenic and vasculogenic cells and can be a novel and highly promising source of cells for cell therapy to treat ischemic cardiovascular diseases.
Kim
Hyongbum
H
Division of Cardiology, Department of Medicine, Emory University School of Medicine, 1639 Pierce Drive, Atlanta, GA 30322, USA.
Cho
Hyun-Jai
HJ
Kim
Sung-Whan
SW
Liu
Bianling
B
Choi
Yong Jin
YJ
Lee
JiYoon
J
Sohn
Young-Doug
YD
Lee
Min-Young
MY
Houge
Mackenzie A
MA
Yoon
Young-sup
YS
D042501:Angiogenic Proteins / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D016026:Bone Marrow Transplantation; D002478:Cells, Cultured; D002630:Chemotactic Factors / Q000378:metabolism; D004195:Disease Models, Animal; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D006614:Hindlimb; D006801:Humans; D016130:Immunophenotyping; D007511:Ischemia / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology / Q000601:surgery*; D017493:Leukocyte Common Antigens / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D018482:Muscle, Skeletal / Q000098:blood supply*; D018919:Neovascularization, Physiologic / Q000235:genetics; D010641:Phenotype; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism*; D013997:Time Factors
D042501:Angiogenic Proteins; D015415:Biomarkers; D002630:Chemotactic Factors; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D049452:Green Fluorescent Proteins; D017493:Leukocyte Common Antigens; C516769:PTPRC protein, human; C516770:Ptprc protein, mouse