Prospective comparative analysis of the angiogenic capacity of monocytes and CD133+ cells in a murine model of hind limb ischemia.
OBJECTIVE
The aim of this study was to compare prospectively the vasculogenic capacity of two cell sources, monocytes and CD133+ cells.


METHODS
Cells were obtained from healthy donors by adherence or magnetic selection. Animals studies were performed in a model of hind limb ischemia and different groups were established according to type and number of cells infused. Revascularization was measured by sequential blood flow analysis using a laser Doppler device and by assessing capillary density in the ischemic muscles. In order to locate the infused cells, immunofluorescence and immunocytochemistry techniques were performed and analyzed by light and confocal microscopy.


RESULTS
During the study period there was a significant improvement in both limb perfusion and capillary density in mice treated with either human monocytes or CD133+ cells (P<0.05) compared with non-treated mice. No cells were detected as incorporated into the vessels when 1 x 10(5) cells were used but with higher doses (1 x 10(6)) a few human cells were observed integrated into the vessels in both groups of treated mice. Supernatants of both cell types showed vascular endothelial growth factor (VEGF), epidermal growth factor (EGF) and platelet-derived growth factor- AB (PDGF-AB) expression.


CONCLUSIONS
Treatment with human monocytes or CD133+ cells improves blood perfusion and capillary density in a murine model and both cell types seem to stimulate vasculogenesis in a fairly similar way.
López-Holgado
Natalia
N
Servicio de Hematología, Hospital Universitario de Salamanca, Salamanca, Spain.
Alberca
Mercedes
M
Sánchez-Guijo
Fermin Martin
FM
Villarón
Eva Maria
EM
Rivas
Jose Vicente
JV
López-Novoa
Jose Miguel
JM
Briñón
Jesus Garcia
JG
Arévalo
Miguel Angel
MA
Oterino
Enrique
E
Santamaría
Carlos
C
San Miguel
Jesus Fernando
JF
del Cañizo
Maria Consuelo
MC
D000071916:AC133 Antigen; D043925:Angiogenesis Inducing Agents / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D002196:Capillaries / Q000473:pathology; D002465:Cell Movement; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D006023:Glycoproteins / Q000378:metabolism*; D006614:Hindlimb / Q000098:blood supply* / Q000473:pathology*; D006801:Humans; D016130:Immunophenotyping; D007511:Ischemia / Q000473:pathology*; D017078:Laser-Doppler Flowmetry; D051379:Mice; D018613:Microscopy, Confocal; D009000:Monocytes / Q000166:cytology*; D009132:Muscles / Q000473:pathology; D018919:Neovascularization, Physiologic; D010455:Peptides / Q000378:metabolism*; D010477:Perfusion; D010641:Phenotype; D012039:Regional Blood Flow; D013194:Staining and Labeling
D000071916:AC133 Antigen; D043925:Angiogenesis Inducing Agents; D015703:Antigens, CD; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse