ArticleThe AAPS journal2018
Screening of Drug-Transporter Interactions in a 3D Microfluidic Renal Proximal Tubule on a Chip.
Article in The AAPS journal, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 2 of them syntheses that pooled it.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
43 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- A systematic review of kidney-on-a-chip-based models to study human renal (patho-)physiology.Disease models & mechanisms · 2023Pooled it
- A quantitative meta-analysis comparing cell models in perfused organ on a chip with static cell cultures.Scientific reports · 2023Pooled it
- Transition to fetal calf serum-free culture enhances kidney proximal tubule cell bioenergetics and allows pharmacological applications.Cell and tissue research · 2026Article
- Construction, evaluation, and applications of renal barrier-on-a-chip system.Bioactive materials · 2026Review
- Human Gut-Brain Interaction Chip for Dissecting the Gut-Derived LPS and Butyrate Regulation of the Blood-Brain Barrier.Biosensors · 2025Article
- Microphysiological systems as an emerging in vitro approach for the evaluation of drug absorption, distribution, metabolism, and excretion and toxicity.Drug metabolism and disposition: the biological fate of chemicals · 2025Review
- Beyond ADME: The Endogenous Functions of Drug Transporters and Its Impact on Human Disease.Pharmaceutics · 2025Review
- Human and rat renal proximal tubule in vitro models for ADME applications.Archives of toxicology · 2025Review
- A Novel Protocol for Culturing Polarized Proximal Tubular Epithelial Cells from Kidney Biopsies: Enhancing Platforms for Drug Excretion and Nephrotoxicity Studies.Journal of xenobiotics · 2025Article
- Proximal tubule-on-chip as a model for predicting cation transport and drug transporter dynamics.Scientific reports · 2025Article
- Advanced Kidney Models In Vitro Using the Established Cell Line Renal Proximal Tubular Epithelial/Telomerase Reverse Transcriptase1 for Nephrotoxicity Assays.Biomimetics (Basel, Switzerland) · 2024Article
- Allogeneic bone marrow mesenchymal stem cell-derived exosomes alleviate human hypoxic AKI-on-a-Chip within a tight treatment window.Stem cell research & therapy · 2024Article
- Construction methods and latest applications of kidney cancer organoids.Oncology reviews · 2024Review
- Revolutionizing nephrology research: expanding horizons with kidney-on-a-chip and beyond.Frontiers in bioengineering and biotechnology · 2024Review
- Organ-On-A-Chip: An Emerging Research Platform.Organogenesis · 2023Review
- Study Models of Drug-Drug Interactions Involving P-Glycoprotein: The Potential Benefit of P-Glycoprotein Modulation at the Kidney and Intestinal Levels.Molecules (Basel, Switzerland) · 2023Review
- Analysis of reproducibility and robustness of a renal proximal tubule microphysiological system OrganoPlate 3-lane 40 for in vitro studies of drug transport and toxicity.Toxicological sciences : an official journal of the Society of Toxicology · 2023Article
- Fluid flow to mimic organ function in 3DAPL bioengineering · 2023Review
- Research Methods and New Advances in Drug-Drug Interactions Mediated by Renal Transporters.Molecules (Basel, Switzerland) · 2023Review
- Apical Medium Flow Influences the Morphology and Physiology of Human Proximal Tubular Cells in a Microphysiological System.Bioengineering (Basel, Switzerland) · 2022Article
Corrections and comments
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Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Drug-transporter interactions could impact renal drug clearance and should ideally be detected in early stages of drug development to avoid toxicity-related withdrawals in later stages. This requires reliable and robust assays for which current high-throughput screenings have, however, poor predictability. Kidney-on-a-chip platforms have the potential to improve predictability, but often lack compatibility with high-content detection platforms. Here, we combined conditionally immortalized proximal tubule epithelial cells overexpressing organic anion transporter 1 (ciPTEC-OAT1) with the microfluidic titer plate OrganoPlate to develop a screenings assay for renal drug-transporter interactions. In this platform, apical localization of F-actin and intracellular tight-junction protein zonula occludens-1 (ZO-1) indicated appropriate cell polarization. Gene expression levels of the drug transporters organic anion transporter 1 (OAT1; SLC22A6), organic cation transporter 2 (OCT2; SLC22A2), P-glycoprotein (P-gp; ABCB1), and multidrug resistance-associated protein 2 and 4 (MRP2/4; ABCC2/4) were similar levels to 2D static cultures. Functionality of the efflux transporters P-gp and MRP2/4 was studied as proof-of-concept for 3D assays using calcein-AM and 5-chloromethylfluorescein-diacetate (CMFDA), respectively. Confocal imaging demonstrated a 4.4 ± 0.2-fold increase in calcein accumulation upon P-gp inhibition using PSC833. For MRP2/4, a 3.0 ± 0.2-fold increased accumulation of glutathione-methylfluorescein (GS-MF) was observed upon inhibition with a combination of PSC833, MK571, and KO143. Semi-quantitative image processing methods for P-gp and MRP2/4 was demonstrated with corresponding Z'-factors of 0.1 ± 0.3 and 0.4 ± 0.1, respectively. In conclusion, we demonstrate a 3D microfluidic PTEC model valuable for screening of drug-transporter interactions that further allows multiplexing of endpoint read-outs for drug-transporter interactions and toxicity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.