An open-access microfluidic model for lung-specific functional studies at an air-liquid interface

Nalayanda, Divya D.; Puleo, Christopher M.; Fulton, William B.; Sharpe, Leilani M.; Wang, Tza Huei; Abdullah, Fizan

doi:10.1007/s10544-009-9325-5

Cited by 86 publications

(87 citation statements)

References 27 publications

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“…Compared to the case of Caco-2 cells, these monolayers represented a weaker epithelial barrier. Lung cell layers in the chip reached a maximum TEER of a 46.4 ± 17.0 cm 2 , and these values were in concordance with our data obtained on A549 culture on Transwell inserts (27.8 ± 2.2 cm 2 ), as well as with literature data for this cell line [33]. Average P app values were 1.45 × 10 −6 cm/s for SF, 1.24 × 10 −6 cm/s for FD and 0.17 × 10 −6 cm/s for EBA markers.…”

Section: Lung Modelsupporting

confidence: 92%

“…In accordance with the functional data, ZO-1 and ␤-catenin staining was not as intensive and continuous as in Caco-2 cells, indicating weaker intercellular junctions. Some lab-on-a-chip models using A549 cells [7,33,34] have already been published, but none of them offers simultaneous cell visualization, measurement of TEER and the flux of marker molecules. Concerning the lung model the chip will enable the establishment of a more complex model of the alveolar capillary unit, by the co-culture of lung epithelial cells with vascular endothelial cells at an air-liquid interface [35].…”

Section: Lung Modelmentioning

confidence: 99%

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A versatile lab-on-a-chip tool for modeling biological barriers

Walter

Valkai

Kincses

et al. 2016

Sensors and Actuators B: Chemical

141

156

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Keywords: Microfluidics Lung and intestinal epithelial cells Endothelial cells Blood-brain barrier PermeabilityTrans-epithelial/endothelial electric resistance a b s t r a c t Models of biological barriers are important to study physiological functions, transport mechanisms, drug delivery and pathologies. However, there are only a few integrated biochips which are able to monitor several of the crucial parameters of cell-culture-based barrier models. The aim of this study was to design and manufacture a simple but versatile device, which allows a complex investigation of barrier functions. The following functions and measurements are enabled simultaneously: co-culture of 2 or 3 types of cells; flow of culture medium; visualization of the entire cell layer by microscopy; real-time transcellular electrical resistance monitoring; permeability measurements. To this end, a poly(dimethylsiloxane)-based biochip with integrated transparent gold electrodes and with a possibility to connect to a peristaltic pump was built. Unlike previous systems, the structure of the device allowed a constant visual observation of cell growth over the whole membrane surface. Morphological characterization of the layers was also accomplished by immunohistochemical staining. The chip was applied to monitor and characterize models of the intestinal and lung epithelial barriers, and the blood-brain barrier. The models were established using human Caco-2 intestinal and A549 lung epithelial cell lines, hCMEC/D3 human brain endothelial cell line and primary rat brain endothelial cells co-cultured with primary astrocytes and brain pericytes. This triple primary co-culture blood-brain barrier model was assembled on a lab-on-a-chip device and investigated under fluid flow for the first time. Such a versatile tool is expected to facilitate the kinetic investigation of various biological barriers.

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Section: Lung Modelsupporting

confidence: 92%

Section: Lung Modelmentioning

confidence: 99%

A versatile lab-on-a-chip tool for modeling biological barriers

Walter

Valkai

Kincses

et al. 2016

Sensors and Actuators B: Chemical

141

156

View full text Add to dashboard Cite

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“…4(e)). Both the maximum TEER and the time to reach this value are consistent with existing reports on A549 cells (Rothen-Rutishauser et al 2005;Blank et al 2006;Nalayanda et al 2009). Moreover, the TEER values for the ALI culture were consistently higher than those for the liquid submerged culture.…”

Section: Physiologic Microfluidic Airway Pressuresupporting

confidence: 91%

“…The increased TEER under the air-liquid interface culture is presumably due to the expression of tight junctional proteins Fig. 3 (a) Physiologic P-V curve of the lung and (b) microfluidic airway differential pressure variation as a function of airflow rate (Blank et al 2006), although the low TEER values suggest only minimal expression levels compared to freshly isolated type II human alveolar cells (Fang et al 2006) and prolonged culture of A549 cells (Nalayanda et al 2009). …”

Section: Physiologic Microfluidic Airway Pressurementioning

confidence: 99%

Epithelium damage and protection during reopening of occluded airways in a physiologic microfluidic pulmonary airway model

Tavana

Zamankhan

Christensen

et al. 2011

Biomed Microdevices

100

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Airways of the peripheral lung are prone to closure at low lung volumes. Deficiency or dysfunction of pulmonary surfactant during various lung diseases compounds this event by destabilizing the liquid lining of small airways and giving rise to occluding liquid plugs in airways. Propagation of liquid plugs in airways during inflation of the lung exerts large mechanical forces on airway cells. We describe a microfluidic model of small airways of the lung that mimics airway architecture, recreates physiologic levels of pulmonary pressures, and allows studying cellular response to repeated liquid plug propagation events. Substantial cellular injury happens due to the propagation of liquid plugs devoid of surfactant. We show that addition of a physiologic concentration of a clinical surfactant, Survanta, to propagating liquid plugs protects the epithelium and significantly reduces cell death. Although the protective role of surfactants has been demonstrated in models of a propagating air finger in liquid-filled airways, this is the first time to study the protective role of surfactants in liquid plugs where fluid mechanical stresses are expected to be higher than in air fingers. Our parallel computational simulations revealed a significant decrease in mechanical forces in the presence of surfactant, confirming the experimental observations. The results support the practice of providing exogenous surfactant to patients in certain clinical settings as a protective mechanism against pathologic flows. More importantly, this platform provides a useful model to investigate various surface tension-mediated lung diseases at the cellular level.

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“…Organoids have been highlighted as one of the major advances in developing suitable models for various specific tissue types. Amongst these are intestine 3 lung [4][5][6] and kidney, 7,8 to name a few. Further models of heart, cartilage and skin, as well as functional systems such as the vascular, endocrine, musculoskeletal, and nervous systems have been reviewed by Benam et al 9 Body-and human-on-a-chip systems further aim to draw connectivity between each of these separate models in order to mimic basic physiological function on a larger scale.…”

Section: Introductionmentioning

confidence: 99%

Tissue engineered organoids for neural network modelling

Kose-Dunn¹,

Fricker²,

Roach³

2017

ATROA

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The increased prevalence of neurological diseases across the world has stimulated a great deal of research into the physiological and pathological brain, both at clinical and pre-clinical level. This has led to the development of many sophisticated tissue engineered neural models, presenting greater cellular complexity to better mimic the central nervous system niche environment. These have been developed with the ambition to improve pre-clinical assessment of pharma and cellular therapies, as well as better understand this tissue type and its function/dysfunction. This review covers the necessary considerations in in vitro model design, along with recent advances in 2Dculture systems, to 3D organoids and bio-artificial organs.

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An open-access microfluidic model for lung-specific functional studies at an air-liquid interface

Cited by 86 publications

References 27 publications

A versatile lab-on-a-chip tool for modeling biological barriers

A versatile lab-on-a-chip tool for modeling biological barriers

Epithelium damage and protection during reopening of occluded airways in a physiologic microfluidic pulmonary airway model

Tissue engineered organoids for neural network modelling

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