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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...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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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. |
format | Online Article Text |
id | pubmed-10525190 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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