Increased number of circulating progenitor cells after implantation of ventricular assist devices.
BACKGROUND
Bone marrow-derived circulating progenitor cells possess tissue repair potential, improving perfusion, left ventricular remodeling, and contractility in experimental models. We quantified and investigated the kinetics of 4 circulating progenitor cell sub-populations on the basis of CD34, CD133, and vascular endothelial growth factor receptor-2 (VEGFR-2) antigen expression.


METHODS
CD34+, CD34+/CD133+/VEGFR-2-, CD34+/CD133+/VEGFR-2+, and CD34+/CD133-/VEGFR-2+ cells were counted in 10 male patients with end-stage congestive heart failure. Five underwent left ventricular/biventricular assist device (LVAD/BiVAD) implantation (VAD group), and 5 were ineligible for VAD implantation (no-VAD group). Peripheral blood was collected at 3 time points for each patient: before, 15, and 60 days after VAD placement in the VAD group and at the same time points in the no-VAD group. Purified CD34+ cells were stained with anti-CD34, anti-CD133, and anti-VEGFR-2 monoclonal antibodies and analyzed by flow cytometry. Serum levels of granulocyte-colony stimulating factor (G-CSF), interleukin-8, vascular endothelial growth factor-alpha (VEGF-alpha), and B-type natriuretic peptide (BNP) were also measured.


RESULTS
In the VAD group the number of CD34+ cells/ml of blood tended to increase, from 159.6 +/- 137.0 at baseline to 428.9 +/- 224.3 at 15 days, and decreased to 343.8 +/- 165.7 at 60 days (p = 0.05 vs no-VAD group). In the other 3 cell populations, no significant differences occurred over time or between groups. A significant interaction between BNP levels and VAD status was observed (p = 0.005): BNP levels decreased over time in VAD patients vs no-VAD patients. G-CSF levels tended to decrease over time in both groups, but without a significant difference (p = 0.3). Serum levels of interleukin-8 and VEGF-alpha over time or between VAD and no-VAD patients were not significantly different.


CONCLUSIONS
After VAD implantation, a transient increase occurs in the number of circulating CD34+ cells, in parallel to a reduction in BNP levels. Release of these cells from the bone marrow may contribute to the improvement of tissue perfusion and cardiac recovery occasionally seen after VAD placement.
Manginas
Athanassios
A
Department of Cardiology, Onassis Cardiac Surgery Center, Athens, Greece. nassoseft@yahoo.com
Tsiavou
Anastasia
A
Sfyrakis
Petros
P
Giamouzis
Gregory
G
Tsourelis
Loukas
L
Leontiadis
Evangelos
E
Degiannis
Dimitrios
D
Cokkinos
Dennis V
DV
Alivizatos
Petros A
PA
D000071916:AC133 Antigen; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D018952:Antigens, CD34 / Q000378:metabolism*; D016022:Case-Control Studies; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D006023:Glycoproteins / Q000378:metabolism; D016179:Granulocyte Colony-Stimulating Factor / Q000097:blood; D006333:Heart Failure / Q000378:metabolism / Q000473:pathology* / Q000628:therapy*; D006353:Heart-Assist Devices; D006412:Hematopoietic Stem Cells / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D016209:Interleukin-8 / Q000097:blood; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010455:Peptides / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000097:blood; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
D000071916:AC133 Antigen; D015703:Antigens, CD; D018952:Antigens, CD34; D006023:Glycoproteins; D016209:Interleukin-8; C000606023:PROM1 protein, human; D010455:Peptides; D042461:Vascular Endothelial Growth Factor A; D020097:Natriuretic Peptide, Brain; D016179:Granulocyte Colony-Stimulating Factor; D040301:Vascular Endothelial Growth Factor Receptor-2