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A Rapid-Patterning 3D Vessel-on-Chip for Imaging and Quantitatively Analyzing Cell–Cell Junction Phenotypes

The blood-brain barrier (BBB) is a dynamic interface that regulates the molecular exchanges between the brain and peripheral blood. The permeability of the BBB is primarily regulated by the junction proteins on the brain endothelial cells. In vitro BBB models have shown great potential for the inves...

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Autores principales: Yan, Li, Dwiggins, Cole W., Gupta, Udit, Stroka, Kimberly M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10525190/
https://www.ncbi.nlm.nih.gov/pubmed/37760182
http://dx.doi.org/10.3390/bioengineering10091080
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author Yan, Li
Dwiggins, Cole W.
Gupta, Udit
Stroka, Kimberly M.
author_facet Yan, Li
Dwiggins, Cole W.
Gupta, Udit
Stroka, Kimberly M.
author_sort Yan, Li
collection PubMed
description The blood-brain barrier (BBB) is a dynamic interface that regulates the molecular exchanges between the brain and peripheral blood. The permeability of the BBB is primarily regulated by the junction proteins on the brain endothelial cells. In vitro BBB models have shown great potential for the investigation of the mechanisms of physiological function, pathologies, and drug delivery in the brain. However, few studies have demonstrated the ability to monitor and evaluate the barrier integrity by quantitatively analyzing the junction presentation in 3D microvessels. This study aimed to fabricate a simple vessel-on-chip, which allows for a rigorous quantitative investigation of junction presentation in 3D microvessels. To this end, we developed a rapid protocol that creates 3D microvessels with polydimethylsiloxane and microneedles. We established a simple vessel-on-chip model lined with human iPSC-derived brain microvascular endothelial-like cells (iBMEC-like cells). The 3D image of the vessel structure can then be “unwrapped” and converted to 2D images for quantitative analysis of cell–cell junction phenotypes. Our findings revealed that 3D cylindrical structures altered the phenotype of tight junction proteins, along with the morphology of cells. Additionally, the cell–cell junction integrity in our 3D models was disrupted by the tumor necrosis factor α. This work presents a “quick and easy” 3D vessel-on-chip model and analysis pipeline, together allowing for the capability of screening and evaluating the cell–cell junction integrity of endothelial cells under various microenvironment conditions and treatments.
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spelling pubmed-105251902023-09-28 A Rapid-Patterning 3D Vessel-on-Chip for Imaging and Quantitatively Analyzing Cell–Cell Junction Phenotypes Yan, Li Dwiggins, Cole W. Gupta, Udit Stroka, Kimberly M. Bioengineering (Basel) Article The blood-brain barrier (BBB) is a dynamic interface that regulates the molecular exchanges between the brain and peripheral blood. The permeability of the BBB is primarily regulated by the junction proteins on the brain endothelial cells. In vitro BBB models have shown great potential for the investigation of the mechanisms of physiological function, pathologies, and drug delivery in the brain. However, few studies have demonstrated the ability to monitor and evaluate the barrier integrity by quantitatively analyzing the junction presentation in 3D microvessels. This study aimed to fabricate a simple vessel-on-chip, which allows for a rigorous quantitative investigation of junction presentation in 3D microvessels. To this end, we developed a rapid protocol that creates 3D microvessels with polydimethylsiloxane and microneedles. We established a simple vessel-on-chip model lined with human iPSC-derived brain microvascular endothelial-like cells (iBMEC-like cells). The 3D image of the vessel structure can then be “unwrapped” and converted to 2D images for quantitative analysis of cell–cell junction phenotypes. Our findings revealed that 3D cylindrical structures altered the phenotype of tight junction proteins, along with the morphology of cells. Additionally, the cell–cell junction integrity in our 3D models was disrupted by the tumor necrosis factor α. This work presents a “quick and easy” 3D vessel-on-chip model and analysis pipeline, together allowing for the capability of screening and evaluating the cell–cell junction integrity of endothelial cells under various microenvironment conditions and treatments. MDPI 2023-09-13 /pmc/articles/PMC10525190/ /pubmed/37760182 http://dx.doi.org/10.3390/bioengineering10091080 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Yan, Li
Dwiggins, Cole W.
Gupta, Udit
Stroka, Kimberly M.
A Rapid-Patterning 3D Vessel-on-Chip for Imaging and Quantitatively Analyzing Cell–Cell Junction Phenotypes
title A Rapid-Patterning 3D Vessel-on-Chip for Imaging and Quantitatively Analyzing Cell–Cell Junction Phenotypes
title_full A Rapid-Patterning 3D Vessel-on-Chip for Imaging and Quantitatively Analyzing Cell–Cell Junction Phenotypes
title_fullStr A Rapid-Patterning 3D Vessel-on-Chip for Imaging and Quantitatively Analyzing Cell–Cell Junction Phenotypes
title_full_unstemmed A Rapid-Patterning 3D Vessel-on-Chip for Imaging and Quantitatively Analyzing Cell–Cell Junction Phenotypes
title_short A Rapid-Patterning 3D Vessel-on-Chip for Imaging and Quantitatively Analyzing Cell–Cell Junction Phenotypes
title_sort rapid-patterning 3d vessel-on-chip for imaging and quantitatively analyzing cell–cell junction phenotypes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10525190/
https://www.ncbi.nlm.nih.gov/pubmed/37760182
http://dx.doi.org/10.3390/bioengineering10091080
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