Nephroscreen. A robust and versatile renal tubule-on-a-chip platform for nephrotoxicity assessment
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Authors
Vriend, Jelle
Vormann, Marianne
Lanz, Henriette
Joore, Jos
Trietsch, Sebastian J.
Russel, Frans
Jacobsen, Björn
Roth, Adrian
Lu, Shuyan
Author (Corporation)
Publication date
03/2021
Typ of student thesis
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Collections
Type
01A - Journal article
Editors
Editor (Corporation)
Supervisor
Parent work
Current Opinion in Toxicology
Special issue
DOI of the original publication
Link
Series
Series number
Volume
25
Issue / Number
Pages / Duration
42-48
Patent number
Publisher / Publishing institution
Elsevier
Place of publication / Event location
Edition
Version
Programming language
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Practice partner / Client
Abstract
Proximal tubule epithelial cells are the main driver of renal transport and secretion of xenobiotics, making them susceptible to drug-induced kidney injury. Cell-based assays are a meaningful alternative to animal testing to detect nephrotoxicity and contribute to the 3Rs (refine, reduce, replace animal experimentation). Here we report on a high-throughput, three-dimensional microfluidic platform (Nephroscreen) to detect drug-induced nephrotoxicity. Toxicologically relevant parameters were used to assess cell viability, functional epithelial barrier integrity, and interactions with specific transporters (P-glycoprotein: P-gp and multidrug resistance–associated protein 2/4: MRP2/4). Nephroscreen allowed the combination of a variety of read-outs, including imaging, extracellularly released markers, intracellular markers, and functional assays. Nephroscreen is compatible with automated pipetting, proved to be amenable to long-term experiments (at least 11 days), and was easily transferred between laboratories. The compelling data originate from several published reports on the development and implementation of this platform to detect nephrotoxicity and drug–transporter interactions. The reports demonstrate that Nephroscreen could be used to detect the nephrotoxic liabilities of the tested compounds. Future directions should include additional test compounds and thorough validation of its performance.
Keywords
Renal proximal tubule, Nephrotoxicity, Drug screening, Drug–transporter interaction, miRNA Kidney-on-a-Chip, Microfluidics
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ISBN
ISSN
2468-2934
2468-2020
2468-2020
Language
English
Created during FHNW affiliation
Yes
Strategic action fields FHNW
Publication status
Published
Review
Peer review of the complete publication
Open access category
Hybrid
License
Citation
Suter-Dick, L., Vriend, J., Vormann, M., Lanz, H., Joore, J., Trietsch, S. J., Russel, F., Jacobsen, B., Roth, A., Lu, S., Polli, J., Naidoo, A., Masereeuw, R., & Wilmer, M. (2021). Nephroscreen. A robust and versatile renal tubule-on-a-chip platform for nephrotoxicity assessment. Current Opinion in Toxicology, 25, 42–48. https://doi.org/10.1016/j.cotox.2021.03.001