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Current State of In vitro Cell-Based Renal Models

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Background: Renal proximal tubule (PT) epithelial cells, expressing uptake and efflux transporters at basolateral and apical membranes, are the location of active renal drug secretion and reabsorption. In addition to singly transfected cells, an in vitro renal cell-based model is a requirement to study the active renal secretion of drugs, drug-drug interactions (DDIs), drug-induced kidney injury, nephrotoxicity holistically and potentially renal replacement therapies.

Objectives: So far, two-dimensional (2D) cell culture of primary and immortalized PT cells has been the only tool to study drugs active secretion, interactions and nephrotoxicity, however a number of in vivo characteristics of cells such as drug transporter expression and function, along with morphological features are lost during in vitro cell culture. Cellular microenvironment, extracellular matrix, cell-cell interactions, microfluidic environment and tubular architecture are the factors lacking in 2D cell culture. Currently, there are a few 3D cell culture platforms mimicking the in vivo conditions of PT cells and thus potentially enabling the necessary factors for the full functional PT cells.

Conclusion: In this review, we address in vivo physiological and morphological characteristics of PT cells, comparing their available sources and remaining in vivo features. In addition, 2D and 3D cell culture platforms and the influence of cell culture architecture on the physiological characteristics of cells are reviewed. Finally, future perspective of 3D models, kidney and multi organs on a chip, generation of kidney organoids, other ex vivo renal models and their capabilities to study drug disposition and in vitro-in vivo extrapolation are described.
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Keywords: Active renal secretion; drug transporters; drug-drug interactions; kidney; nephrotoxicity; organ on chip; renal model; renal proximal tubule cells

Document Type: Review Article

Publication date: April 1, 2018

This article was made available online on February 7, 2018 as a Fast Track article with title: "Current State of In vitro Cell-Based Renal Models".

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  • Current Drug Metabolism aims to cover all the latest and outstanding developments in drug metabolism and disposition. The journal serves as an international forum for the publication of timely reviews in drug metabolism. Current Drug Metabolism is an essential journal for academic, clinical, government and pharmaceutical scientists who wish to be kept informed and up-to-date with the latest and most important developments. The journal covers the following areas:

    In vitro systems including CYP-450; enzyme induction and inhibition; drug-drug interactions and enzyme kinetics; pharmacokinetics, toxicokinetics, species scaling and extrapolations; P-glycoprotein and transport carriers; target organ toxicity and interindividual variability; drug metabolism and disposition studies; extrahepatic metabolism; phase I and phase II metabolism; recent developments for the identification of drug metabolites and adducts.
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