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A perfused renal human organ culture model: impact of monocyte attack
Rainer Voisard1, Regine Baur, Tina Herter
1Department of Internal Medicine II - Cardiology, University Medical Center Ulm, Germany. rainer.voisard@uni-ulm.de
Background:
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).
Material/Methods:
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.
Results:
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.
Conclusion:
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.
Insights
Human monocytes (MCs) primarily accumulated in the adventitia, not the artery wall, in a novel perfused renal organ culture model. This study provides insights into monocyte behavior in atherosclerosis and restenosis research.
Area of Science:
- Cardiovascular Biology
- Translational Medicine
- Organoid Models
Background:
- Atherosclerosis and restenosis involve monocyte (MC) interactions with arterial walls.
- This study introduces a perfused human renal organ culture model for investigating monocyte behavior.
Purpose of the Study:
- To investigate the behavior and localization of human monocytes in a perfused human renal organ culture model.
- To assess the initial inflammatory response and smooth muscle cell proliferation in response to monocytes.
Main Methods:
- Renal artery segments were obtained from nephrectomies and established in a closed-loop perfusion system.
- Human monocytes (5x10^5) were introduced into the culture medium for 24 hours.
- Immunohistological staining was performed at various time points (0-72 hours) to analyze monocyte distribution and cell proliferation.
Main Results:
- Monocytes predominantly accumulated in the adventitia, with minimal presence in the intima and media.
- No significant increase in smooth muscle cell proliferation was observed in the artery wall during the three-day perfusion period.
- The model demonstrated steady perfusion at 1.6 mL/min, maintaining viability for MC analysis.
Conclusions:
- Steady perfusion of the renal organ culture model is crucial for studying monocyte roles in atherosclerosis and restenosis.
- The model provides a valuable ex vivo platform for understanding inflammation in vascular diseases.
- Further research can adapt this model to explore the complex pathophysiology of atherosclerosis and restenosis.
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