Die Transplantation von humanen endothelialen und angiogenen Zellen verbessert die linksventrikuläre Funktion im Myokardinfarktmodell der Nacktratte
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vor 17 Jahren
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.
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.
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