Local erythropoietin and endothelial progenitor cells improve regional cardiac function in acute myocardial infarction

<p>Abstract</p> <p>Background</p> <p>Expanded endothelial progenitor cells (eEPC) improve global left ventricular function in experimental myocardial infarction (MI). Erythropoietin beta (EPO) applied together with eEPC may improve regional myocardial function even further by anti-apoptotic and cardioprotective effects. Aim of this study was to evaluate intramyocardial application of eEPCs and EPO as compared to eEPCs or EPO alone in experimental MI.</p> <p>Methods and Results</p> <p>In vitro experiments revealed that EPO dosed-dependently decreased eEPC and leukocyte apoptosis. Moreover, in the presence of EPO mRNA expression in eEPC of proangiogenic and proinflammatory mediators measured by TaqMan PCR was enhanced. Experimental MI was induced by ligation and reperfusion of the left anterior descending coronary artery of nude rats (n = 8-9). After myocardial transplantation of eEPC and EPO CD68+ leukocyte count and vessel density were enhanced in the border zone of the infarct area. Moreover, apoptosis of transplanted CD31 + TUNEL + eEPC was decreased as compared to transplantation of eEPCs alone. Regional wall motion of the left ventricle was measured using Magnetic Resonance Imaging. After injection of eEPC in the presence of EPO regional wall motion significantly improved as compared to injection of eEPCs or EPO alone.</p> <p>Conclusion</p> <p>Intramyocardial transplantation of eEPC in the presence of EPO during experimental MI improves regional wall motion. This was associated with an increased local inflammation, vasculogenesis and survival of the transplanted cells. Local application of EPO in addition to cell therapy may prove beneficial in myocardial remodeling.</p

Abstract 4374: G-CSF Treatment Improves Cardiac Function In postmyocarditic Cardiomyopathy By Enhanced Circulation And Homing Of CD34+ Progenitor Cell Populations

Objective : Recently, it was shown that the physiologic repair mechanism of mobilization and homing of bone marrow-derived stem cells (BMCs) is impaired in dilated cardiomyopathy. In our study we aimed to analyze circulation and homing of CD34 + progenitor cell populations in a murine model of dilated cardiomyopathy due to coxsackie virus B3 (CVB3) induced myocarditis and the influence of G-CSF treatment on BMC homing and cardiac function. Methods and Results : First, SWR/J (H-2q)-mice were infected by intraperitoneal injection of 10 5 pfu CVB3. Healthy, age-matched SWR/J (H-2q)-mice served as controls. 12 weeks after infection, DCM was verified by MRI/Millar-tip-catheter and histology. In DCM mice, CD34 + BMC populations (CD34 + CD31 + , CD34 + Sca-1 + , CD34 + c-kit + and CD34 + CXCR-4 + ) measured by flow cytometry were significantly increased in peripheral blood, decreased in bone marrow and remained unchanged in the hearts in comparison to controls. Different from ischemic heart diseases, myocardial homing factors (SDF-1, SCF, HIF-1a, VCAM and HGF) assessed by real-time PCR were not upregulated in the CVB3-DCM group. Finally, 18 DCM-CVB3 mice were analyzed by MRI 8 weeks after CVB3 infection and randomized into G-CSF-or saline-treatment (100 μg/20μl s.c. daily for 2× 5 days). 12 weeks after infection, cardiac function was assessed using MRI: Change of ejection fraction was significantly better in the G-CSF-group compared to the controls (4.1±1.8 vs. −2.5±2.2%; p=0.03). The improvement of cardiac function was associated with enhanced homing of BMC subpopulations. Conclusions : We have shown that postmyocarditic cardiomyopathy is associated with a reduced migration of BMCs to the cardiomyopathic hearts due to a lack of increase of homing factors. This defect can partly be overcome by G-CSF-administration resulting in an increased number of stem cells in the myocardium and leading to a moderately improved cardiac function. Therefore our data provides new insights in the pathogenesis of dilated cariomyopathy and presents a promising non-invasive approach to ameliorate heart failure. <jats:p /