Transepithelial electrical resistance (TEER): a functional parameter to monitor the quality of oviduct epithelial cells cultured on filter supports

Chen, Shuai; Einspanier, Ralf; Schoen, Jennifer

doi:10.1007/s00418-015-1351-1

Cited by 133 publications

(99 citation statements)

References 26 publications

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“…Mgf was analysed in both the A and B compartments to calculate the value of Papp (Figure 11). The TEER values were continuously recorded while performing experiment, showing miniscule reduction (i.e., <10%) in TEER value on the treated cells wrt the control cells which indicated that there was slight opening of the tight junctions of Caco-2 cells, signifying paracellular transport (Sha et al, 2005;Chen et al, 2015;Laksitorini et al, 2015).…”

Section: Bidirectional Permeability Assaymentioning

confidence: 99%

Enhancing biopharmaceutical attributes of phospholipid complex-loaded nanostructured lipidic carriers of mangiferin: Systematic development, characterization and evaluation

Khurana

Bansal

Beg

et al. 2017

International Journal of Pharmaceutics

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Mangiferin (Mgf), largely expressed out from the leaves and stem bark of Mango, is a potent antioxidant. However, its in vivo activity gets tremendously reduced owing to poor aqueous solubility and inconsistent gastrointestinal absorption, high hepatic first-pass metabolism and high P-gp efflux. The current research work, therefore, was undertaken to overcome the biopharmaceutical hiccups by developing the Mgfphospholipid complex (PLCs) loaded in nanostructured lipidic carriers (NLCs). The PLCs and NLCs were prepared using refluxing, solvent evaporation and hot emulsification technique, respectively with various molar ratios of Mgf and Phospholipon 90 G, i.e., 1:1; 1:2; and 1:3. The complex was evaluated for various physicochemical parameters like drug content (96.57%), aqueous solubility (25-fold improved) and oil-water partition coefficient (10-fold enhanced). Diverse studies on the prepared complex using FTIR, DSC, PXRD and SEM studies ratified the formation of PLCs at 1:1 ratio. The PLCs were further incorporated onto NLCs, which were systematically optimized employing a face centered cubic design (FCCD), while evaluating for particle size, zeta potential, encapsulation efficiency and in vitro drug release as the CQAs. Caco-2 cell line indicated insignificant cytotoxicity, and P-gp efflux, bi-directional permeability model and in situ perfusion studies specified enhanced intestinal permeation parameters. In vivo pharmacokinetic studies revealed notable increase in the values of Cmax (4.7-fold) and AUC (2.1-fold), respectively, from PLCs-loaded NLCs vis-à-vis Mgf solution. In a nutshell, the promising results observed from the present research work signified boosted biopharmaceutical potential of the optimized PLCs-loaded NLCs for potentially augmenting the therapeutic efficacy of Mgf.

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Section: Bidirectional Permeability Assaymentioning

confidence: 99%

Enhancing biopharmaceutical attributes of phospholipid complex-loaded nanostructured lipidic carriers of mangiferin: Systematic development, characterization and evaluation

Khurana

Bansal

Beg

et al. 2017

International Journal of Pharmaceutics

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“…Trans‐epithelial electrical resistance (TEER) measurements are widely used in biology and tissue engineering to determine epithelial and endothelial cell health and membrane integrity. These measurements give an indirect, noninvasive assessment of the permeability of cellular tight junctions and ultimately the barrier function of a cellular monolayer or 3D tissues (Chen, Einspanier, & Schoen, 2015; Schmitz et al, 2018). There are several variables known to affect the final readout including electrode size, measurement temperature, media formulation, time in culture, and cell passage number, making it difficult to standardize measurements (Elbrecht, Long, & Hickman, 2018; Srinivasan et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

“…Trans-epithelial electrical resistance (TEER) measurements are widely used in biology and tissue engineering to determine epithelial and endothelial cell health and membrane integrity. These measurements give an indirect, noninvasive assessment of the permeability of cellular tight junctions and ultimately the barrier function of a cellular monolayer or 3D tissues (Chen, Einspanier, & Schoen, 2015;Schmitz et al, 2018).…”

mentioning

confidence: 99%

Three‐Dimensional (3D) cell culture monitoring: Opportunities and challenges for impedance spectroscopy

León

Pupovac

McArthur

2020

Biotech & Bioengineering

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Three‐dimensional (3D) cell culture has developed rapidly over the past 5–10 years with the goal of better replicating human physiology and tissue complexity in the laboratory. Quantifying cellular responses is fundamental in understanding how cells and tissues respond during their growth cycle and in response to external stimuli. There is a need to develop and validate tools that can give insight into cell number, viability, and distribution in real‐time, nondestructively and without the use of stains or other labelling processes. Impedance spectroscopy can address all of these challenges and is currently used both commercially and in academic laboratories to measure cellular processes in 2D cell culture systems. However, its use in 3D cultures is not straight forward due to the complexity of the electrical circuit model of 3D tissues. In addition, there are challenges in the design and integration of electrodes within 3D cell culture systems. Researchers have used a range of strategies to implement impedance spectroscopy in 3D systems. This review examines electrode design, integration, and outcomes of a range of impedance spectroscopy studies and multiparametric systems relevant to 3D cell cultures. While these systems provide whole culture data, impedance tomography approaches have shown how this technique can be used to achieve spatial resolution. This review demonstrates how impedance spectroscopy and tomography can be used to provide real‐time sensing in 3D cell cultures, but challenges remain in integrating electrodes without affecting cell culture functionality. If these challenges can be addressed and more realistic electrical models for 3D tissues developed, the implementation of impedance‐based systems will be able to provide real‐time, quantitative tracking of 3D cell culture systems.

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“…Several methods exist to assess endothelial/epithelial cell monolayer confluence and barrier quality, including determination of fluid filtration coefficient (K f ), hydraulic conductivity (L p ), apparent solute permeability (P app ), and transepithelial electrical resistance (TEER) [40,41]. In our work, we have selected to measure the apparent solute permeability (P app ) through a drug transport assay, as it is the most direct measurement for evaluating our variable of interest: the permeability of the Caco-2 monolayer to paracellularly transported drugs [42].…”

Section: Introductionmentioning

confidence: 99%

Improvement of paracellular transport in the Caco-2 drug screening model using protein-engineered substrates

et al. 2017

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The Caco-2 assay has achieved wide popularity among pharmaceutical companies in the past two decades as an in vitro method for estimation of in vivo oral bioavailability of pharmaceutical compounds during preclinical characterization. Despite its popularity, this assay suffers from a severe under-prediction of the transport of drugs which are absorbed paracellularly, that is, which pass through the cell-cell tight junctions of the absorptive cells of the small intestine. Here, we propose that simply replacing the collagen I matrix employed in the standard Caco-2 assay with an engineered matrix, we can control cell morphology and hence regulate the cell-cell junctions that dictate paracellular transport. Specifically, we use a biomimetic engineered extracellular matrix (eECM) that contains modular protein domains derived from two ECM proteins found in the small intestine, fibronectin and elastin. This eECM allows us to independently tune the density of cell-adhesive RGD ligands presented to Caco-2 cells as well as the mechanical stiffness of the eECM. We observe that lower amounts of RGD ligand presentation as well as decreased matrix stiffness results in Caco-2 morphologies that more closely resemble primary small intestinal epithelial cells than Caco-2 cells cultured on collagen. Additionally, these matrices result in Caco-2 monolayers with decreased recruitment of actin to the apical junctional complex and increased expression of claudin-2, a tight junction protein associated with higher paracellular permeability that is highly expressed throughout the small intestine. Consistent with these morphological differences, drugs known to be paracellularly transported in vivo exhibited significantly improved transport rates in this modified Caco-2 model. As expected, permeability of transcellularly transported drugs remained unaffected. Thus, we have demonstrated a method of improving the physiological accuracy of the Caco-2 assay that could be readily adopted by pharmaceutical companies without major changes to their current testing protocols.

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Transepithelial electrical resistance (TEER): a functional parameter to monitor the quality of oviduct epithelial cells cultured on filter supports

Cited by 133 publications

References 26 publications

Enhancing biopharmaceutical attributes of phospholipid complex-loaded nanostructured lipidic carriers of mangiferin: Systematic development, characterization and evaluation

Enhancing biopharmaceutical attributes of phospholipid complex-loaded nanostructured lipidic carriers of mangiferin: Systematic development, characterization and evaluation

Three‐Dimensional (3D) cell culture monitoring: Opportunities and challenges for impedance spectroscopy

Improvement of paracellular transport in the Caco-2 drug screening model using protein-engineered substrates

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