Increased Number of Circulating Progenitor Cells After Implantation of Ventricular Assist Devices
Received 28 November 2008; received in revised form 17 March 2009; accepted 7 April 2009. published online 15 May 2009.
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-α (VEGF-α), 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-α 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.
aDepartment of Cardiology, Onassis Cardiac Surgery Center, Athens, Greece
bCardiothoracic Surgery & Heart Transplantation, Onassis Cardiac Surgery Center, Athens, Greece
cMolecular Immunopathology and Histocompatibility Laboratory, Onassis Cardiac Surgery Center, Athens, Greece
Reprint requests: Athanassios Manginas, MD, FACC, FESC, Onassis Cardiac Surgery Center, Department of Cardiology, 356 Sygrou Ave, Kallithea, Athens, 176 74, Greece. Telephone: +30-210-949-3235. Fax: +30-210-949-3235
ABSTRACT