Combined administration of G-CSF and GM-CSF stimulates monocyte-derived pro-angiogenic cells in patients with acute myocardial infarction.
Mobilization of endothelial progenitor cells has been suggested to contribute to neo-vascularization of ischemic organs. Aim of this study was to investigate whether the combination of granulocyte colony stimulating factor (G-CSF) and granulocyte-macrophage (GM)-CSF may influence the expansion of circulating KDR+ cells in patients with acute myocardial infarction (AMI). KDR+ cells significantly increased in peripheral blood of AMI patients treated with G-CSF and GM-CSF compared to untreated patients. This KDR+ cells population was CD14+ but not CD34+ or CD133+. CD14+/KDR+ cells were also obtained in vitro by culturing mononuclear cells from healthy donors in a Rotary Cell Culture System in the presence of G-CSF + GM-CSF, but not of the individual growth factors. CD14+/KDR+ cells, obtained from patients or from in vitro culture, co-expressed hematopoietic (CD45, CD14) and endothelial markers (CD31, CD105, and VE-cadherin). CD14+/KDR+, but not CD14+/KDR- cells, stimulated the organization of human microvascular endothelial cells into capillary-like structures on Matrigel both in vitro and in vivo. The combination of G-CSF and GM-CSF induced a CD14+/KDR+ cell population with potential pro-angiogenic properties.
Bruno
Stefania
S
Department of Internal Medicine, Research Center for Experimental Medicine (CeRMS), University of Torino, Italy.
Bussolati
Benedetta
B
Scacciatella
Paolo
P
Marra
Sebastiano
S
Sanavio
Fiorella
F
Tarella
Corrado
C
Camussi
Giovanni
G
D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D018952:Antigens, CD34 / Q000096:biosynthesis; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology; D006023:Glycoproteins / Q000096:biosynthesis; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D066298:In Vitro Techniques; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis; D051379:Mice; D016513:Mice, SCID; D009000:Monocytes / Q000378:metabolism*; D009203:Myocardial Infarction / Q000378:metabolism*; D009389:Neovascularization, Pathologic; D010455:Peptides; D013234:Stem Cells / Q000166:cytology; D015854:Up-Regulation
D000071916:AC133 Antigen; D015703:Antigens, CD; D018952:Antigens, CD34; D006023:Glycoproteins; D018950:Lipopolysaccharide Receptors; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor