Nephroscreen. A robust and versatile renal tubule-on-a-chip platform for nephrotoxicity assessment
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Autor:innen
Vriend, Jelle
Vormann, Marianne
Lanz, Henriette
Joore, Jos
Trietsch, Sebastian J.
Russel, Frans
Jacobsen, Björn
Roth, Adrian
Lu, Shuyan
Autor:in (Körperschaft)
Publikationsdatum
03/2021
Typ der Arbeit
Studiengang
Typ
01A - Beitrag in wissenschaftlicher Zeitschrift
Herausgeber:innen
Herausgeber:in (Körperschaft)
Betreuer:in
Übergeordnetes Werk
Current Opinion in Toxicology
Themenheft
DOI der Originalpublikation
Link
Reihe / Serie
Reihennummer
Jahrgang / Band
25
Ausgabe / Nummer
Seiten / Dauer
42-48
Patentnummer
Verlag / Herausgebende Institution
Elsevier
Verlagsort / Veranstaltungsort
Auflage
Version
Programmiersprache
Abtretungsempfänger:in
Praxispartner:in/Auftraggeber:in
Zusammenfassung
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.
Schlagwörter
Renal proximal tubule, Nephrotoxicity, Drug screening, Drug–transporter interaction, miRNA Kidney-on-a-Chip, Microfluidics
Fachgebiet (DDC)
Veranstaltung
Startdatum der Ausstellung
Enddatum der Ausstellung
Startdatum der Konferenz
Enddatum der Konferenz
Datum der letzten Prüfung
ISBN
ISSN
2468-2934
2468-2020
2468-2020
Sprache
Englisch
Während FHNW Zugehörigkeit erstellt
Ja
Publikationsstatus
Veröffentlicht
Begutachtung
Peer-Review der ganzen Publikation
Open Access-Status
Hybrid
Lizenz
Zitation
SUTER-DICK, Laura, Jelle VRIEND, Marianne VORMANN, Henriette LANZ, Jos JOORE, Sebastian J. TRIETSCH, Frans RUSSEL, Björn JACOBSEN, Adrian ROTH, Shuyan LU, Joseph POLLI, Anita NAIDOO, Rosalinde MASEREEUW und Martijn WILMER, 2021. Nephroscreen. A robust and versatile renal tubule-on-a-chip platform for nephrotoxicity assessment. Current Opinion in Toxicology. März 2021. Bd. 25, S. 42–48. DOI 10.1016/j.cotox.2021.03.001. Verfügbar unter: https://doi.org/10.26041/fhnw-4112