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

Key processes of atherosclerosis and restenosis are triggered and/or modified by the contact of human monocytes (MCs) with the inner layers of the arterial vessel wall. This is the first report on monocyte attack in a perfused renal human organ culture model (perfused renal HOC-model). Parts of the renal arteries were extracted during routine nephrectomies. A closed loop system was established by fixing the segments between two hard plastic tubes and connecting the distal endings of the hard plastic tubes with soft plastic tubes. 5x10(5) 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. Perfusion of the model with culture medium was performed with a steady flow 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 flow perfusion, no stimulation of smooth muscle cell proliferation in the artery wall was detected. 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 inflammation in the pathophysiology of atherosclerosis and restenosis.