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Permeability across a novel microfluidic blood-tumor barrier model
BACKGROUND: The lack of translatable in vitro blood-tumor barrier (BTB) models creates challenges in the development of drugs to treat tumors of the CNS and our understanding of how the vascular changes at the BBB in the presence of a tumor. METHODS: In this study, we characterize a novel microfluid...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5260004/ https://www.ncbi.nlm.nih.gov/pubmed/28114946 http://dx.doi.org/10.1186/s12987-017-0050-9 |
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author | Terrell-Hall, Tori B. Ammer, Amanda G. Griffith, Jessica I. G. Lockman, Paul R. |
author_facet | Terrell-Hall, Tori B. Ammer, Amanda G. Griffith, Jessica I. G. Lockman, Paul R. |
author_sort | Terrell-Hall, Tori B. |
collection | PubMed |
description | BACKGROUND: The lack of translatable in vitro blood-tumor barrier (BTB) models creates challenges in the development of drugs to treat tumors of the CNS and our understanding of how the vascular changes at the BBB in the presence of a tumor. METHODS: In this study, we characterize a novel microfluidic model of the BTB (and BBB model as a reference) that incorporates flow and induces shear stress on endothelial cells. Cell lines utilized include human umbilical vein endothelial cells co-cultured with CTX-TNA2 rat astrocytes (BBB) or Met-1 metastatic murine breast cancer cells (BTB). Cells were capable of communicating across microfluidic compartments via a porous interface. We characterized the device by comparing permeability of three passive permeability markers and one marker subject to efflux. RESULTS: The permeability of Sulforhodamine 101 was significantly (p < 0.05) higher in the BTB model (13.1 ± 1.3 × 10(−3), n = 4) than the BBB model (2.5 ± 0.3 × 10(−3), n = 6). Similar permeability increases were observed in the BTB model for molecules ranging from 600 Da to 60 kDa. The function of P-gp was intact in both models and consistent with recent published in vivo data. Specifically, the rate of permeability of Rhodamine 123 across the BBB model (0.6 ± 0.1 × 10(−3), n = 4), increased 14-fold in the presence of the P-gp inhibitor verapamil (14.7 ± 7.5 × 10(−3), n = 3) and eightfold with the addition of Cyclosporine A (8.8 ± 1.8 × 10(−3), n = 3). Similar values were noted in the BTB model. CONCLUSIONS: The dynamic microfluidic in vitro BTB model is a novel commercially available model that incorporates shear stress, and has permeability and efflux properties that are similar to in vivo data. |
format | Online Article Text |
id | pubmed-5260004 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-52600042017-01-26 Permeability across a novel microfluidic blood-tumor barrier model Terrell-Hall, Tori B. Ammer, Amanda G. Griffith, Jessica I. G. Lockman, Paul R. Fluids Barriers CNS Research BACKGROUND: The lack of translatable in vitro blood-tumor barrier (BTB) models creates challenges in the development of drugs to treat tumors of the CNS and our understanding of how the vascular changes at the BBB in the presence of a tumor. METHODS: In this study, we characterize a novel microfluidic model of the BTB (and BBB model as a reference) that incorporates flow and induces shear stress on endothelial cells. Cell lines utilized include human umbilical vein endothelial cells co-cultured with CTX-TNA2 rat astrocytes (BBB) or Met-1 metastatic murine breast cancer cells (BTB). Cells were capable of communicating across microfluidic compartments via a porous interface. We characterized the device by comparing permeability of three passive permeability markers and one marker subject to efflux. RESULTS: The permeability of Sulforhodamine 101 was significantly (p < 0.05) higher in the BTB model (13.1 ± 1.3 × 10(−3), n = 4) than the BBB model (2.5 ± 0.3 × 10(−3), n = 6). Similar permeability increases were observed in the BTB model for molecules ranging from 600 Da to 60 kDa. The function of P-gp was intact in both models and consistent with recent published in vivo data. Specifically, the rate of permeability of Rhodamine 123 across the BBB model (0.6 ± 0.1 × 10(−3), n = 4), increased 14-fold in the presence of the P-gp inhibitor verapamil (14.7 ± 7.5 × 10(−3), n = 3) and eightfold with the addition of Cyclosporine A (8.8 ± 1.8 × 10(−3), n = 3). Similar values were noted in the BTB model. CONCLUSIONS: The dynamic microfluidic in vitro BTB model is a novel commercially available model that incorporates shear stress, and has permeability and efflux properties that are similar to in vivo data. BioMed Central 2017-01-23 /pmc/articles/PMC5260004/ /pubmed/28114946 http://dx.doi.org/10.1186/s12987-017-0050-9 Text en © The Author(s) 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Terrell-Hall, Tori B. Ammer, Amanda G. Griffith, Jessica I. G. Lockman, Paul R. Permeability across a novel microfluidic blood-tumor barrier model |
title | Permeability across a novel microfluidic blood-tumor barrier model |
title_full | Permeability across a novel microfluidic blood-tumor barrier model |
title_fullStr | Permeability across a novel microfluidic blood-tumor barrier model |
title_full_unstemmed | Permeability across a novel microfluidic blood-tumor barrier model |
title_short | Permeability across a novel microfluidic blood-tumor barrier model |
title_sort | permeability across a novel microfluidic blood-tumor barrier model |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5260004/ https://www.ncbi.nlm.nih.gov/pubmed/28114946 http://dx.doi.org/10.1186/s12987-017-0050-9 |
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