Temporal monitoring of differentiated human airway epithelial cells using microfluidics
Temporal monitoring of differentiated human airway epithelial cells using microfluidics
The airway epithelium is exposed to a variety of harmful agents during breathing and appropriate cellular responses are essential to maintain tissue homeostasis. Recent evidence has highlighted the contribution of epithelial barrier dysfunction in the development of many chronic respiratory diseases. Despite intense research efforts, the responses of the airway barrier to environmental agents are not fully understood, mainly due to lack of suitable in vitro models that recapitulate the complex in vivo situation accurately. Using an interdisciplinary approach, we describe a novel dynamic 3D in vitro model of the airway epithelium, incorporating fully differentiated primary human airway epithelial cells at the air-liquid interface and a basolateral microfluidic supply of nutrients simulating the interstitial flow observed in vivo. Through combination of the microfluidic culture system with an automated fraction collector the kinetics of cellular responses by the airway epithelium to environmental agents can be analysed at the early phases for the first time and with much higher sensitivity compared to common static in vitro models. Following exposure of primary differentiated epithelial cells to pollen we show that CXCL8/IL-8 release is detectable within the first 2h and peaks at 4-6h under microfluidic conditions, a response which was not observed in conventional static culture conditions. Such a microfluidic culture model is likely to have utility for high resolution temporal profiling of toxicological and pharmacological responses of the airway epithelial barrier, as well as for studies of disease mechanisms.
1-13
Blume, Cornelia
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Reale, Riccardo
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Held, Marie
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Millar, Timothy M.
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Collins, Jane E.
be0e66f1-3036-47fa-9d7e-914c48710ba4
Davies, Donna E.
7de8fdc7-3640-4e3a-aa91-d0e03f990c38
Morgan, Hywel
de00d59f-a5a2-48c4-a99a-1d5dd7854174
Swindle, Emily J.
fe393c7a-a513-4de4-b02e-27369bd7e84f
5 October 2015
Blume, Cornelia
aa391c64-8718-4238-906b-d6bb1551a07b
Reale, Riccardo
c7651c37-e622-45aa-a0e1-595d35ca4b2c
Held, Marie
45e89d4d-9087-4e18-8a6e-344e7c904be7
Millar, Timothy M.
ec88510c-ad88-49f6-8b2d-4277c84c1958
Collins, Jane E.
be0e66f1-3036-47fa-9d7e-914c48710ba4
Davies, Donna E.
7de8fdc7-3640-4e3a-aa91-d0e03f990c38
Morgan, Hywel
de00d59f-a5a2-48c4-a99a-1d5dd7854174
Swindle, Emily J.
fe393c7a-a513-4de4-b02e-27369bd7e84f
Blume, Cornelia, Reale, Riccardo, Held, Marie, Millar, Timothy M., Collins, Jane E., Davies, Donna E., Morgan, Hywel and Swindle, Emily J.
(2015)
Temporal monitoring of differentiated human airway epithelial cells using microfluidics.
PLoS ONE, 10 (10), , [e0139872].
(doi:10.1371/journal.pone.0139872).
(PMID:26436734)
Abstract
The airway epithelium is exposed to a variety of harmful agents during breathing and appropriate cellular responses are essential to maintain tissue homeostasis. Recent evidence has highlighted the contribution of epithelial barrier dysfunction in the development of many chronic respiratory diseases. Despite intense research efforts, the responses of the airway barrier to environmental agents are not fully understood, mainly due to lack of suitable in vitro models that recapitulate the complex in vivo situation accurately. Using an interdisciplinary approach, we describe a novel dynamic 3D in vitro model of the airway epithelium, incorporating fully differentiated primary human airway epithelial cells at the air-liquid interface and a basolateral microfluidic supply of nutrients simulating the interstitial flow observed in vivo. Through combination of the microfluidic culture system with an automated fraction collector the kinetics of cellular responses by the airway epithelium to environmental agents can be analysed at the early phases for the first time and with much higher sensitivity compared to common static in vitro models. Following exposure of primary differentiated epithelial cells to pollen we show that CXCL8/IL-8 release is detectable within the first 2h and peaks at 4-6h under microfluidic conditions, a response which was not observed in conventional static culture conditions. Such a microfluidic culture model is likely to have utility for high resolution temporal profiling of toxicological and pharmacological responses of the airway epithelial barrier, as well as for studies of disease mechanisms.
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journal.pone.0139872.PDF
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More information
Accepted/In Press date: 18 September 2015
e-pub ahead of print date: 5 October 2015
Published date: 5 October 2015
Organisations:
Clinical & Experimental Sciences
Identifiers
Local EPrints ID: 389844
URI: http://eprints.soton.ac.uk/id/eprint/389844
ISSN: 1932-6203
PURE UUID: f66102ea-1a95-42cc-8eeb-3de84ddb7f40
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Date deposited: 16 Mar 2016 15:15
Last modified: 15 Mar 2024 03:35
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Contributors
Author:
Riccardo Reale
Author:
Marie Held
Author:
Timothy M. Millar
Author:
Hywel Morgan
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