Dataset Information

Real-time observation of leukocyte-endothelium interactions in tissue-engineered blood vessel.

ABSTRACT: Human cell-based 3D tissue constructs play an increasing role in disease modeling and drug screening. Inflammation, atherosclerosis, and many autoimmune disorders involve the interactions between immune cells and blood vessels. However, it has been difficult to image and model these interactions under realistic conditions. In this study, we fabricated a perfusion and imaging chamber to allow the real-time visualization of leukocyte perfusion, adhesion, and migration inside a tissue-engineered blood vessel (TEBV). We monitored the elevated monocyte adhesion to the TEBV wall and transendothelial migration (TEM) as the TEBV endothelium was activated by the inflammatory cytokine TNF-?. We demonstrated that treatment with anti-TNF-? or an NF-kB signaling pathway inhibitor would attenuate the endothelium activation and reduce the number of leukocyte adhesion (>74%) and TEM events (>87%) close to the control. As the first demonstration of real-time imaging of dynamic cellular events within a TEBV, this work paves the way for drug screening and disease modeling in TEBV-associated microphysiological systems.

SUBMITTER: Chen Z

PROVIDER: S-EPMC6055475 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Real-time observation of leukocyte-endothelium interactions in tissue-engineered blood vessel.

Chen Z Z Tang M M Huang D D Jiang W W Li M M Ji H H Park J J Xu B B Atchison L J LJ Truskey G A GA Leong K W KW

Lab on a chip 20180701 14

Human cell-based 3D tissue constructs play an increasing role in disease modeling and drug screening. Inflammation, atherosclerosis, and many autoimmune disorders involve the interactions between immune cells and blood vessels. However, it has been difficult to image and model these interactions under realistic conditions. In this study, we fabricated a perfusion and imaging chamber to allow the real-time visualization of leukocyte perfusion, adhesion, and migration inside a tissue-engineered bl ...[more]

PMID: 29927449

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Project description:ObjectiveIntravascular stents are commonly used to treat occluded arteries during coronary heart disease. After coronary stent implantation, endothelial cells grow over the stent, which is referred to as re-endothelialization. Re-endothelialization prevents blood from clotting on the stent surface and is a good predictor of stent success. Blood vessel mimics (BVMs) are in vitro tissue-engineered models of human blood vessels that may be used to preclinically test stents for re-endothelialization. BVMs have been developed in straight geometries. However, the United States Food and Drug Administration recommends that devices intended to treat coronary occlusions be preclinically tested in bent and bifurcated vessels due to the complex geometries of native coronary arteries. The main objectives of this study were to develop and characterize BVMs in complex geometries.DesignBioreactors were designed and constructed so that BVMs could be cultivated in bent (>45°) and bifurcated geometries. Human umbilical vein endothelial cells were sodded onto complex-shaped scaffolds, and the resulting BVMs were characterized for cell deposition. For a final proof of concept, a coronary stent was deployed in a severely angulated BVM.ResultsThe new bioreactors were easy to use and mounting scaffolds in complex geometries in the bioreactors was successful. After sodding scaffolds with cells, there were no statistically significant differences between the cell densities along the length of the BVMs, on the top and bottom halves of the BVMs, or on the inner and outer halves of the BVMs. This suggests cells deposited evenly throughout the scaffolds, resulting in consistent complex-geometry BVMs. Also, a coronary stent was successfully deployed in a severely angulated BVM.ConclusionsBioreactors can be constructed for housing complex-shaped vessels. BVMs can be developed in the complex geometries observed in native coronary arteries with endothelial cells evenly dispersed throughout BVM lumens.

Dataset Information

Real-time observation of leukocyte-endothelium interactions in tissue-engineered blood vessel.

Publications

Real-time observation of leukocyte-endothelium interactions in tissue-engineered blood vessel.

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