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In Vitro 3D Cell-Cultured Arterial Models for Studying Vascular Drug Targeting Under Flow
Published on: March 14, 2021
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Modeling early stage atherosclerosis in a primary human vascular microphysiological system
Xu Zhang1, Muath Bishawi1,2, Ge Zhang3,4
1Department of Biomedical Engineering, Duke University, Durham, NC, 27708, USA.
Nature Communications
|October 28, 2020
Summary
Researchers developed a novel in vitro model of early atherosclerosis using human tissue-engineered blood vessels (TEBVs). This model mimics disease progression and evaluates drug efficacy on vascular functions, aiding clinical therapy development.
Area of Science:
- Biomedical Engineering
- Cardiovascular Research
- Vascular Biology
Background:
- Atherosclerosis research requires advanced in vitro models to accurately predict clinical outcomes.
- Existing models often fail to replicate the complex microenvironment of human vasculature.
Purpose of the Study:
- To develop and validate a novel in vitro model of early atherosclerosis.
- To assess the utility of this model in evaluating therapeutic interventions for atherosclerosis.
Main Methods:
- Fabrication and perfusion of multi-layer, arteriole-scale human tissue-engineered blood vessels (TEBVs) using plastic compression.
- Exposure of TEBVs to enzyme-modified low-density-lipoprotein (eLDL) and TNFα under physiological shear stress.
- Evaluation of endothelial cell activation, monocyte accumulation, foam cell formation, and vasoactivity.
Main Results:
- TEBVs successfully mimicked early atherosclerosis, showing endothelial activation, monocyte accumulation, and foam cell formation.
- The model demonstrated reduced vasoactivity and altered nitric oxide (NO) production upon eLDL exposure.
- Pretreatment with lovastatin or a P2Y11 inhibitor (NF157) effectively reduced monocyte accumulation and blocked foam cell formation.
- Perfusion with whole blood increased monocyte adhesion, further validating the model's relevance.
Conclusions:
- The developed TEBV model provides a robust platform for studying early atherosclerosis in vitro.
- This model allows for the assessment of specific drug effects on vascular functions, offering insights not obtainable through traditional in vivo methods.
