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Weidl, Eliane (2007): Die Transplantation von humanen endothelialen und angiogenen Zellen verbessert die linksventrikuläre Funktion im Myokardinfarktmodell der Nacktratte. Dissertation, LMU München: Tierärztliche Fakultät



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.