O3	Vessels transmigration of stem cells depends on activation of the endothelium.
1A.Schmidt, 2D.Ladage, 2K.Brixius, 3F-J.Klinz, 4T.Schinköthe, 5U.Mehlhorn, 2R.H.G.Schwinger, 3K.Addicks, 1W.Bloch
1German Sport University Cologne, Dept. of Molecular and Cellular Sport Medicine, Cologne, DE; 2University of Cologne, Dept. of Internal Medicine III, Cologne, DE; 3University of Cologne, Institute for Anatomy, Cologne, DE; 4University of Cologne, Dept. of Internal Medicine I, Cologne, DE; 5University of Cologne, Clinic for Cardiothoracic Surgery, Cologne, DE.

Bone marrow derived adult pluripotent stem cells (BMSCs) demonstrate the ability to differentiate into various mesenchymal tissues. Therefore these cells are important approaches for tissue regeneration, especially for the therapy of myocardial infarction. For these therapeutic uses it is crucial that the BMSCs are able to transmigrate over the endothelial barrier and have the ability to leave blood vessels after application. Nevertheless there is very little known about the underlying mechanisms of BMSC-migration. During our study we focused especially on the interaction of BMSCs with the endothelium. Therefore we performed co-culture experiments on the one site as well as isolated heart perfusion on the other site to analyse the direct interaction between both cell types. Then again we analysed the indirect interaction among both cell types by soluble factors. Therefore endothelial cells were treated with conditioned stem cell medium. Following the activation of endothelium was analysed by signal transduction as well as morphological changes. The indirect interaction between both cell types reveals broad changes on the level of signal transduction, with a transient up regulation of eNOS and AKT-kinase. By analysing the direct interaction an approach between endothelial and stem cells was observable by the verification of Connexin 43 clustering as well as by the integration of BMSCs into the endothelial monolayer. Similar results we observed by isolated heart perfusion. Besides the activation of the endothelium and morphological changes of the endothelium, we were able to observe the transmigration of stem cells through the endothelial barrier. Summarizing we can show that BMSCs lead to an activation of the endothelium as well as to broad morphological changes and changes of the level of signal transduction what can implicate a transmigration of stem cells.

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