Organs-on-chips with integrated electrodes for trans-epithelial electrical resistance (TEER) measurements of human epithelial barrier function

Henry, Olivier; Villenave, Rémi; Cronce, Michael J.; Leineweber, William D.; Benz, Maximilian A.; Ingber, Donald E.

doi:10.1039/c7lc00155j

Cited by 347 publications

(332 citation statements)

References 30 publications

(38 reference statements)

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“…We argue that, the specialized ECM microenvironment together with fluid flow conditions in In‐OC guides the epithelial morphogenesis directing the cells both towards the mucus‐producing cell phenotype as well as the enterocyte phenotype providing a 3D tissue with a more physiological functionality (Kim & Ingber, ). Another important aspect is the state of the permeability barrier obtained by the measure of the TEER as the electrical resistance across an epithelium is directly related to the formation of robust tight junctions between neighboring cells (Henry et al, ). To perform electrical measurements, a gasket was inserted in the sealed chamber on the apical side of the biological samples, to ensure that the medium remains confined in its place.…”

Section: Resultsmentioning

confidence: 99%

Intestine‐on‐chip device increases ECM remodeling inducing faster epithelial cell differentiation

Gregorio

Corrado

Sbrescia

et al. 2019

Biotech & Bioengineering

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An intestine‐on‐chip has been developed to study intestinal physiology and pathophysiology as well as intestinal transport absorption and toxicity studies in a controlled and human similar environment. Here, we report that dynamic culture of an intestine‐on‐chip enhances extracellular matrix (ECM) remodeling of the stroma, basement membrane production and speeds up epithelial differentiation. We developed a three‐dimensional human intestinal stromal equivalent composed of human intestinal subepithelial myofibroblasts embedded in their own ECM. Then, we cultured human colon carcinoma‐derived cells in both static and dynamic conditions in the opportunely designed microfluidic system until the formation of a well‐oriented epithelium. This low cost and handy microfluidic device allows to qualitatively and quantitatively detect epithelial polarization and mucus production as well as monitor barrier function and ECM remodeling after nutraceutical treatment.

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Section: Resultsmentioning

confidence: 99%

Intestine‐on‐chip device increases ECM remodeling inducing faster epithelial cell differentiation

Gregorio

Corrado

Sbrescia

et al. 2019

Biotech & Bioengineering

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“…Indeed, most devices are featured with 2 electrodes only, making it impossible to eliminate solution resistance in the electrochemical cell and thus are more sensitive to any interference coming from junction potentials. Furthermore, only two of these systems (Booth and Kim, 2012;Henry et al, 2017) allow optical monitoring of cells during culture.…”

Section: Introductionmentioning

confidence: 99%

Real-time cellular impedance monitoring and imaging of biological barriers in a dual-flow membrane bioreactor

Cacopardo

Costa

Giusti

et al. 2019

Biosensors and Bioelectronics

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The generation of physiologically relevant in-vitro models of biological barriers can play a key role in understanding human diseases and in the development of more predictive methods for assessing toxicity and drug or nutrient absorption. Here, we present an advanced cell culture system able to mimic the dynamic environment of biological barriers while monitoring cell behaviour through real-time impedance measurements and imaging. It consists of a fluidic device with an apical and a basal flow compartment separated by a semi-permeable membrane. The main features of the device are the integration of a transepithelial electrical impedance (TEEI) meter and transparent windows for optical monitoring within a dual flow system. Caco-2 cells were cultured in the TEEI bioreactor under both flow and static conditions. Although no differences in the expression of peripheral actin and occludin were visible, the cells in dynamic conditions developed higher impedance values at low frequencies, indicative of a higher paracellular electrical impedance and thus suggesting accelerated barrier and tight junction formation with respect to the static cultures. TEEI measurements at high frequency also enabled monitoring the evolution of transcellular impedance during culture. The cells subject to flow showed a typical RC behaviour, while the controls showed minimal capacitive behaviour, again highlighting the differences between flow and static conditions.

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“…Moreover, 3-D bioprinting techniques are facilitating complex spatial patterning of cells and scaffolds (352). Although traditional electrodes used for TEER measurements do not accommodate the small culture area of most OAC models (220), recent studies have integrated custom electrodes (353).…”

Section: Limitations and Future Directions Of 3-d Organoidsmentioning

confidence: 99%

Modeling Host-Pathogen Interactions in the Context of the Microenvironment: Three-Dimensional Cell Culture Comes of Age

et al. 2018

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Tissues and organs provide the structural and biochemical landscapes upon which microbial pathogens and commensals function to regulate health and disease. While flat two-dimensional (2-D) monolayers composed of a single cell type have provided important insight into understanding host-pathogen interactions and infectious disease mechanisms, these reductionist models lack many essential features present in the native host microenvironment that are known to regulate infection, including three-dimensional (3-D) architecture, multicellular complexity, commensal microbiota, gas exchange and nutrient gradients, and physiologically relevant biomechanical forces (e.g., fluid shear, stretch, compression). A major challenge in tissue engineering for infectious disease research is recreating this dynamic 3-D microenvironment (biological, chemical, and physical/mechanical) to more accurately model the initiation and progression of host-pathogen interactions in the laboratory. Here we review selected 3-D models of human intestinal mucosa, which represent a major portal of entry for infectious pathogens and an important niche for commensal microbiota. We highlight seminal studies that have used these models to interrogate host-pathogen interactions and infectious disease mechanisms, and we present this literature in the appropriate historical context. Models discussed include 3-D organotypic cultures engineered in the rotating wall vessel (RWV) bioreactor, extracellular matrix (ECM)-embedded/organoid models, and organ-on-a-chip (OAC) models. Collectively, these technologies provide a more physiologically relevant and predictive framework for investigating infectious disease mechanisms and antimicrobial therapies at the intersection of the host, microbe, and their local microenvironments.

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Organs-on-chips with integrated electrodes for trans-epithelial electrical resistance (TEER) measurements of human epithelial barrier function

Cited by 347 publications

References 30 publications

Intestine‐on‐chip device increases ECM remodeling inducing faster epithelial cell differentiation

Intestine‐on‐chip device increases ECM remodeling inducing faster epithelial cell differentiation

Real-time cellular impedance monitoring and imaging of biological barriers in a dual-flow membrane bioreactor

Modeling Host-Pathogen Interactions in the Context of the Microenvironment: Three-Dimensional Cell Culture Comes of Age

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