P596The complexity of coronary artery disease influences number and function of stem cells in the bone marrow

Abstract

Purpose. Despite the observed therapeutic benefits of autologous bone marrow (BM) cell transplantation in patients with ischemic heart disease, the efficacy of this approach could be hampered by intrinsic BM dysfunction. We investigated whether BM cellularity and function is affected by the severity of coronary artery disease (CAD). Methods. 23 CAD patients, undergoing coronary artery bypass surgery (age 62±9 yrs; LVEF 52±15%), were stratified according to their Syntax score (≤ and > 13), which is used to assess complexity of coronary lesions. BM samples were obtained peri-operatively. In vitro functional analysis of isolated BM-derived mononuclear cells (MNC) included (i) migratory capacity towards SDF-1α and VEGF, (ii) number of granulocyte-macrophage colony forming units (GM-CFU) and (iii) burst forming units erythroid (BFU-E). Numbers of hematopoietic stem cells (HSC, CD45dimCD34+SSClow) and endothelial progenitor cells (EPC, CD45dimCD34+KDR+) were quantified by flow cytometry. Results. Patients with Syntax score >13 showed a significantly impaired migratory capacity of BM-MNC (34.9±8.2% vs. 26.9±7.7%; p=0.03) and a reduced number of EPC (2233±1944 EPC/106 BM-MNC vs. 472±464 EPC/106 BM-MNC; p=0.01) compared to patients with Syntax score ≤ 13. GM-CFU, BFU-E and HSC numbers did not differ between groups. An inverse correlation was found between age and the number of GM-CFU (r= -0.487; p=0.03) and BFU-E (r= -0.505; p=0.02). Furthermore, our data revealed a relation between reduced renal function (eGFR, 77.4±18.0 ml/min) and number of HSC (r=0.433; p=0.039) and EPC (r=0.466; p=0.029). Conclusions. Migratory capacity of BM-MNC is impaired in patients with severe CAD, which could lead to a reduced therapeutic efficacy of autologous stem cell therapy in this patient group. In addition, EPC number decreases as the complexity of CAD increases. Not only CAD complexity, but also age and renal function are identified as influencing factors on the bone marrow function and stem cell populations.