Permeability across a novel microfluidic blood-tumor barrier model
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. In this study, we characterize a novel microfluidic model of the BTB (...
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| Veröffentlicht in: | Fluids and barriers of the CNS 2017-01, Vol.14 (1), p.3-3, Article 3 |
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| creator | Terrell-Hall, Tori B Ammer, Amanda G Griffith, Jessica I G Lockman, Paul R |
| description | 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.
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.
The permeability of Sulforhodamine 101 was significantly (p |
| doi_str_mv | 10.1186/s12987-017-0050-9 |
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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.
The permeability of Sulforhodamine 101 was significantly (p < 0.05) higher in the BTB model (13.1 ± 1.3 × 10
, n = 4) than the BBB model (2.5 ± 0.3 × 10
, 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
, n = 4), increased 14-fold in the presence of the P-gp inhibitor verapamil (14.7 ± 7.5 × 10
, n = 3) and eightfold with the addition of Cyclosporine A (8.8 ± 1.8 × 10
, n = 3). Similar values were noted in the BTB model.
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.</description><identifier>ISSN: 2045-8118</identifier><identifier>EISSN: 2045-8118</identifier><identifier>DOI: 10.1186/s12987-017-0050-9</identifier><identifier>PMID: 28114946</identifier><language>eng</language><publisher>England: BioMed Central Ltd</publisher><subject>Analysis ; Animals ; Astrocytes - metabolism ; ATP-Binding Cassette, Sub-Family B, Member 1 - metabolism ; Blood-Brain Barrier - metabolism ; Cancer metastasis ; Capillary Permeability ; Cell Line ; Coculture Techniques ; Diffusion ; Endothelium ; Human Umbilical Vein Endothelial Cells ; Humans ; Kinetics ; Mice ; Microfluidics ; Microfluidics - methods ; Models, Cardiovascular ; Models, Neurological ; Neoplasms - blood supply ; Neoplasms - metabolism ; Permeability ; Physiological aspects ; Rats</subject><ispartof>Fluids and barriers of the CNS, 2017-01, Vol.14 (1), p.3-3, Article 3</ispartof><rights>COPYRIGHT 2017 BioMed Central Ltd.</rights><rights>Copyright BioMed Central 2017</rights><rights>The Author(s) 2017</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c525t-8ccaab4902d56cd936c0f9874d5951f365f59dcfb568b9827c409cf2aca332923</citedby><cites>FETCH-LOGICAL-c525t-8ccaab4902d56cd936c0f9874d5951f365f59dcfb568b9827c409cf2aca332923</cites><orcidid>0000-0002-6995-9944</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5260004/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5260004/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,729,782,786,866,887,27933,27934,53800,53802</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28114946$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Terrell-Hall, Tori B</creatorcontrib><creatorcontrib>Ammer, Amanda G</creatorcontrib><creatorcontrib>Griffith, Jessica I G</creatorcontrib><creatorcontrib>Lockman, Paul R</creatorcontrib><title>Permeability across a novel microfluidic blood-tumor barrier model</title><title>Fluids and barriers of the CNS</title><addtitle>Fluids Barriers CNS</addtitle><description>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.
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.
The permeability of Sulforhodamine 101 was significantly (p < 0.05) higher in the BTB model (13.1 ± 1.3 × 10
, n = 4) than the BBB model (2.5 ± 0.3 × 10
, 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
, n = 4), increased 14-fold in the presence of the P-gp inhibitor verapamil (14.7 ± 7.5 × 10
, n = 3) and eightfold with the addition of Cyclosporine A (8.8 ± 1.8 × 10
, n = 3). Similar values were noted in the BTB model.
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.</description><subject>Analysis</subject><subject>Animals</subject><subject>Astrocytes - metabolism</subject><subject>ATP-Binding Cassette, Sub-Family B, Member 1 - metabolism</subject><subject>Blood-Brain Barrier - metabolism</subject><subject>Cancer metastasis</subject><subject>Capillary Permeability</subject><subject>Cell Line</subject><subject>Coculture Techniques</subject><subject>Diffusion</subject><subject>Endothelium</subject><subject>Human Umbilical Vein Endothelial Cells</subject><subject>Humans</subject><subject>Kinetics</subject><subject>Mice</subject><subject>Microfluidics</subject><subject>Microfluidics - methods</subject><subject>Models, Cardiovascular</subject><subject>Models, Neurological</subject><subject>Neoplasms - blood supply</subject><subject>Neoplasms - metabolism</subject><subject>Permeability</subject><subject>Physiological aspects</subject><subject>Rats</subject><issn>2045-8118</issn><issn>2045-8118</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><recordid>eNptUttqHSEUldLShDQf0JcyUCh9mVQddfSlkIReAoHmoX0Wx0uOwRlTnQnk77unJ0nPKXEjXvbaS_ZyIfSW4BNCpPhUCVWybzGBiTlu1Qt0SDHjrYT0y539ATqu9QbDYKzHgr5GBxTumWLiEJ1d-TJ6M8QU5_vG2JJrbUwz5TufmjHCOaQlumibIeXs2nkZc2kGU0r0pRmz8-kNehVMqv74YT1Cv75--Xn-vb388e3i_PSytZzyuZXWGjMwhanjwjrVCYsDdMAcV5yETvDAlbNh4EIOStLeMqxsoMaarqOKdkfo85b3dhlG76yf5mKSvi1xNOVeZxP1fmaKG32d7zSnYm0eCD4-EJT8e_F11mOs1qdkJp-XqkFVIrDslATo-_-gN3kpE7S3olgvO9GLf6hrk7yOU8jwrl1J9SmTWED0ClAnz6AgnAeB8-RDhPu9gg87BRtv0rypOS1zzFPdB5It8O-3FR-exCBYrybRW5NoMIleTaLXmne7Kj5VPFqi-wMUwrVF</recordid><startdate>20170123</startdate><enddate>20170123</enddate><creator>Terrell-Hall, Tori B</creator><creator>Ammer, Amanda G</creator><creator>Griffith, Jessica I G</creator><creator>Lockman, Paul R</creator><general>BioMed Central Ltd</general><general>BioMed Central</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-6995-9944</orcidid></search><sort><creationdate>20170123</creationdate><title>Permeability across a novel microfluidic blood-tumor barrier model</title><author>Terrell-Hall, Tori B ; Ammer, Amanda G ; Griffith, Jessica I G ; Lockman, Paul R</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c525t-8ccaab4902d56cd936c0f9874d5951f365f59dcfb568b9827c409cf2aca332923</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Analysis</topic><topic>Animals</topic><topic>Astrocytes - metabolism</topic><topic>ATP-Binding Cassette, Sub-Family B, Member 1 - metabolism</topic><topic>Blood-Brain Barrier - metabolism</topic><topic>Cancer metastasis</topic><topic>Capillary Permeability</topic><topic>Cell Line</topic><topic>Coculture Techniques</topic><topic>Diffusion</topic><topic>Endothelium</topic><topic>Human Umbilical Vein Endothelial Cells</topic><topic>Humans</topic><topic>Kinetics</topic><topic>Mice</topic><topic>Microfluidics</topic><topic>Microfluidics - methods</topic><topic>Models, Cardiovascular</topic><topic>Models, Neurological</topic><topic>Neoplasms - blood supply</topic><topic>Neoplasms - metabolism</topic><topic>Permeability</topic><topic>Physiological aspects</topic><topic>Rats</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Terrell-Hall, Tori B</creatorcontrib><creatorcontrib>Ammer, Amanda G</creatorcontrib><creatorcontrib>Griffith, Jessica I G</creatorcontrib><creatorcontrib>Lockman, Paul R</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Access via ProQuest (Open Access)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Fluids and barriers of the CNS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Terrell-Hall, Tori B</au><au>Ammer, Amanda G</au><au>Griffith, Jessica I G</au><au>Lockman, Paul R</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Permeability across a novel microfluidic blood-tumor barrier model</atitle><jtitle>Fluids and barriers of the CNS</jtitle><addtitle>Fluids Barriers CNS</addtitle><date>2017-01-23</date><risdate>2017</risdate><volume>14</volume><issue>1</issue><spage>3</spage><epage>3</epage><pages>3-3</pages><artnum>3</artnum><issn>2045-8118</issn><eissn>2045-8118</eissn><abstract>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.
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.
The permeability of Sulforhodamine 101 was significantly (p < 0.05) higher in the BTB model (13.1 ± 1.3 × 10
, n = 4) than the BBB model (2.5 ± 0.3 × 10
, 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
, n = 4), increased 14-fold in the presence of the P-gp inhibitor verapamil (14.7 ± 7.5 × 10
, n = 3) and eightfold with the addition of Cyclosporine A (8.8 ± 1.8 × 10
, n = 3). Similar values were noted in the BTB model.
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.</abstract><cop>England</cop><pub>BioMed Central Ltd</pub><pmid>28114946</pmid><doi>10.1186/s12987-017-0050-9</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0002-6995-9944</orcidid><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; BioMedCentral; DOAJ Directory of Open Access Journals; SpringerNature Journals; PubMed Central; Springer Nature OA/Free Journals; PubMed Central Open Access |
| subjects | Analysis Animals Astrocytes - metabolism ATP-Binding Cassette, Sub-Family B, Member 1 - metabolism Blood-Brain Barrier - metabolism Cancer metastasis Capillary Permeability Cell Line Coculture Techniques Diffusion Endothelium Human Umbilical Vein Endothelial Cells Humans Kinetics Mice Microfluidics Microfluidics - methods Models, Cardiovascular Models, Neurological Neoplasms - blood supply Neoplasms - metabolism Permeability Physiological aspects Rats |
| title | Permeability across a novel microfluidic blood-tumor barrier model |
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