Engineering and monitoring cellular barrier models

Yeste, José; Illa, Xavi; Álvarez, Mar; Villa, Rosa

doi:10.1186/s13036-018-0108-5

Cited by 68 publications

(59 citation statements)

References 138 publications

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“…The integrity of the monolayer in the bioreactors was con rmed by the TEEI measurements ( Figure 4C), which follow a typical RC circuit trend. Indeed, the cell monolayer can be represented by an equivalent electric circuit composed of the resistive paracellular pathway and cell capacity (transcellular pathway) in parallel (27,28). At lower frequencies the capacitor becomes progressively more charged and current ow across it decreases, thus ions ow paracellulary (i.e.…”

Section: Discussionmentioning

confidence: 99%

A dynamic in-vitro model of the intestinal epithelium for the investigation of P-glycoprotein activity

Costa

Almonti

Cacopardo

et al. 2020

Preprint

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Abstract Multidrug resistance is still an obstacle for chemotherapeutic treatments. One of the proteins involved in this phenomenon is the P-glycoprotein, P-gp, which is known to be responsible for the efflux of therapeutic substances from the cell cytoplasm. To date, the identification of a drug that can efficiently inhibit P-gp activity remains a challenge, nevertheless some studies have identified natural compounds suitable for that purpose. Amongst them, curcumin has shown an inhibitory effect on the protein in in vitro studies using Caco-2 cells.To understand if physiological flow can modulate membrane protein activity, we studied the uptake of a P-gp substrate under static and dynamic conditions. Caco-2 cells were cultured in bioreactors and in Transwells and the basolateral transport of Rhodamine-123 assessed in the two systems as a function of P-gp activity. Experiments were performed with and without pre-treatment of the cells with an extract of curcumin or an arylmethyloxy-phenyl derivative to evaluate the inhibitory effect of the natural substance with respect to a synthetic compound.The results indicated that the P-gp activity of the cells cultured in the bioreactors was intrinsically lower, and that the effect of both natural and synthetic inhibitors was up modulated by the presence of flow. Our study underlies the fact that the use of more sophisticated and physiologically relevant in vitro models can bring new insights on the therapeutic effects of natural substances such as curcumin.

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Section: Discussionmentioning

confidence: 99%

A dynamic in-vitro model of the intestinal epithelium for the investigation of P-glycoprotein activity

Costa

Almonti

Cacopardo

et al. 2020

Preprint

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“…Electrical resistance rises from the high transport resistance of ions through a cell barrier and can, therefore, be used as a measure of the integrity of a barrier. The TEER is often measured with a chopstick-like electrode (Yeste et al, 2018).…”

Section: Teermentioning

confidence: 99%

“…Monitoring the development and integrity of cell barriers during maturation and experiments is crucial for all stud-ies performed on barriers. Methods for accessing the barrier permeability are based on the transport of tracer substances, e.g., mannose or fluorescent dyes, immunofluorescent staining of proteins related to the tight junction complex, or measurement of the electrical resistance (Yeste et al, 2018). In this article, we focus on the latter considering that electric resistance is noninvasive, comparably easy to perform, and the most widely used method (Srinivasan et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Cell barrier characterization in transwell inserts by electrical impedance spectroscopy

Linz

Djeljadini

Steinbeck

et al. 2020

Biosensors and Bioelectronics

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We describe an impedance-based method for cell barrier integrity testing. A four-electrode electrical impedance spectroscopy (EIS) setup can be realized by simply connecting a commercial chopstick-like electrode (STX-1) to a potentiostat allowing monitoring cell barriers cultivated in transwell inserts. Subsequent electric circuit modeling of the electrical impedance results the capacitive properties of the barrier next to the well-known transepithelial electrical resistance (TEER). The versatility of the new method was analyzed by the EIS analysis of a Caco-2 monolayer in response to (a) different membrane coating materials, (b) two different permeability enhancers ethylene glycol-bis(2-aminoethylether)-N,N,N',N'-tetraacetic acid (EGTA) and saponin, and (c) sonoporation. For the different membrane coating materials, the TEERs of the standard and new protocol coincide and increase during cultivation, while the capacitance shows a distinct maximum for three different surface materials (no coating, Matrigel ® , and collagen I). The permeability enhancers cause a decline in the TEER value, but only saponin alters the capacitance of the cell layer by two orders of magnitude. Hence, cell layer capacitance and TEER represent two independent properties characterizing the monolayer. The use of commercial chopstick-like electrodes to access the impedance of a barrier cultivated in transwell inserts enables remarkable insight into the behavior of the cellular barrier with no extra work for the researcher. This simple method could evolve into a standard protocol used in cell barrier research.

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“…The compartmentalization facilitates the integration of multiple cell types, and different configurations can be achieved depending on the tissue architecture one wants to recapitulate. 94 Cells can be placed as a monolayer at the interface between two chambers or encapsulated in a 3D matrix. Some systems allow direct cell-ECM contacts without the use of any artificial membrane, which is particularly useful for investigating the influence of matrix properties on cell behavior.…”

Section: Conventional In Vitro Models Of the Brbmentioning

confidence: 99%

Organ-On-A-Chip Technologies for Advanced Blood–Retinal Barrier Models

Ragelle

Gonçalves

Kustermann

et al. 2020

Journal of Ocular Pharmacology and Therapeutics

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The blood-retinal barrier (BRB) protects the retina by maintaining an adequate microenvironment for neuronal function. Alterations of the junctional complex of the BRB and consequent BRB breakdown in disease contribute to a loss of neuronal signaling and vision loss. As new therapeutics are being developed to prevent or restore barrier function, it is critical to implement physiologically relevant in vitro models that recapitulate the important features of barrier biology to improve disease modeling, target validation, and toxicity assessment. New directions in organ-on-a-chip technology are enabling more sophisticated 3-dimensional models with flow, multicellularity, and control over microenvironmental properties. By capturing additional biological complexity, organs-on-chip can help approach actual tissue organization and function and offer additional tools to model and study disease compared with traditional 2-dimensional cell culture. This review describes the current state of barrier biology and barrier function in ocular diseases, describes recent advances in organ-on-a-chip design for modeling the BRB, and discusses the potential of such models for ophthalmic drug discovery and development.

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Engineering and monitoring cellular barrier models

Cited by 68 publications

References 138 publications

A dynamic in-vitro model of the intestinal epithelium for the investigation of P-glycoprotein activity

A dynamic in-vitro model of the intestinal epithelium for the investigation of P-glycoprotein activity

Cell barrier characterization in transwell inserts by electrical impedance spectroscopy

Organ-On-A-Chip Technologies for Advanced Blood–Retinal Barrier Models

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