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30 January 2007

A perfused renal human organ culture model: Impact of monocyte attack

Rainer Voisard, Regine Baur, Tina Herter, Uwe Krüger, Jürgen Breul, Lutz Keller, Vinzenz Hombach

Med Sci Monit 2007; 13(2): CR82-88 :: ID: 473765

Abstract

Background: Key processes of atherosclerosis and restenosis are triggered and/or modifi ed by the contact of human monocytes (MCs) with the inner layers of the arterial vessel wall. This is the fi rst report on monocyte attack in a perfused renal human organ culture model (perfused renal HOC-model).
Material/Methods: Parts of the renal arteries were extracted during routine nephrectomies. A closed loop system was established by fi xing the segments between two hard plastic tubes and connecting the distal endings
of the hard plastic tubes with soft plastic tubes. 5×10[sup]5[/sup] human MCs were added to the culture medium for a period of 24 h. Immunohistological staining was carried out before adding the MCs and after 2, 24, 48, and 72 hours.
Results: Perfusion of the model with culture medium was performed with a steady fl ow of 1.6 ml/min. One, two, and three days after adding the intravascular MCs, almost no extravascular MCs were detected.
Although the number of MCs was merely slightly increased on the endothelium, in the plaque-intima, and in the media, a large number of MCs was detected in the adventitia. During the three-day period of steady fl ow perfusion, no stimulation of smooth muscle cell proliferation in the artery
wall was detected.
Conclusions: Steady perfusion of the renal HOC-model is an important step in the attempt to adapt human ex vivo models to the various roles of infl ammation in the pathophysiology of atherosclerosis and restenosis.

Keywords: Coronary Restenosis - etiology, Chemotaxis, Leukocyte, Cell Adhesion, Atherosclerosis - etiology, Kidney - physiopathology, Models, Cardiovascular, Monocytes - physiology, Organ Culture Techniques, Perfusion

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