Die Transplantation von humanen endothelialen und angiogenen Zellen verbessert die linksventrikuläre Funktion im Myokardinfarktmodell der Nacktratte

Mortality due to acute myocardial infarction has been drastically reduced by optimal means of intervention, but loss of myocytes is leading to heart failure later on and with it to an impaired quality and expectancy of the patient´s life. The research of adult stem and progenitor cells gave hope that transplantation of these cells into infarcted tissue could restore its contractile function. One potentially therapeutically viable kind of cells are endothelial progenitor cells, but there are only limited numers of cells available. Also at present there is no consensus how best to obtain endothelial progenitor cells. In this study we used two different procedures of culturing endothelial progenitor cells from peripheral blood that had been applied regularly in earlier studies and compared both cell types with each other, regarding their manner of growth, their morphology, expression of surface markers and their angiogenic potential on matrigel. It turned out that cells, which were obtained from unfractioned mononuclear cells, survived only for a short period of time in culture, showed little proliferation and expressed different kinds of markers. We called these cells angiogenic cells. Cells which were obtained from CD34+ mononuclear cells on the other hand survived in culture for up to 20 weeks, were highly proliferative and showed a homogenous expression of markers. We refered to these cells as endothelial cells. Both kinds of cells were transplanted into the myocardium of athymic nude rats, after experimental infarction and the ventricular function was assessed via sonography. After 14 days a significant improvement of the ventricular function was found in both cell groups compared to the control group that had only received culture medium, but no significant effect on the size of the infarction was found. Assessment of left ventricular morphology showed a significant decrease of ventricular dilation and wall thinning in infarction area. Vessel formation was studied after 3 and 14 days, using markers for smooth muscle cells and von Willebrand factor-positive cells. No differences were found in angiogenesis. These results show that different ways of obtaining endothelial progenitor cells lead to distinctly different cell populations which however have very similar effects after transplantation into the infarcted area, which is an improvement of ventricular function and remodeling, probably caused by paracrine effects

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