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dc.contributor.authorSuter-Dick, Laura
dc.contributor.authorMauch, Linda
dc.contributor.authorRamp, D
dc.contributor.authorCaj, Michaela
dc.contributor.authorVormann, Marianne K.
dc.contributor.authorHutter, Simon
dc.contributor.authorLanz, H.L.
dc.contributor.authorVried, J.
dc.contributor.authorMasereeuw, R.
dc.contributor.authorWilmer, Martijn J.
dc.date.accessioned2018-12-13T09:57:23Z
dc.date.available2018-12-13T09:57:23Z
dc.date.issued2018-07
dc.identifier.doi10.1208/s12248-018-0245-2.
dc.identifier.urihttp://hdl.handle.net/11654/26973
dc.description.abstractDrug-induced kidney injury is often observed in the clinics and can lead to long-term organ failure. In this work, we evaluated a novel in vitro system that aims at detecting whether compounds can cause renal proximal tubule damage in man. For this, we implemented organotypic cultures of human conditionally immortalized proximal tubule epithelial cells overexpressing the organic anion transporter 1 (ciPTEC-OAT1) in a three-channel OrganoPlate under microfluidic conditions. Cells were exposed to four known nephrotoxicants (cisplatin, tenofovir, cyclosporine A, and tobramycin). The effect on cell viability and NAG release into the medium was determined. A novel panel of four miRNAs (mir-21, mir-29a, mir-34a, and mir-192) was selected as potential biomarkers of proximal tubule damage. After nephrotoxicant treatment, miRNA levels in culture medium were earlier indicators than cell viability (WST-8 assay) and outperformed NAG for proximal tubule damage. In particular, mir-29a, mir-34a, and mir-192 were highly reproducible between experiments and across compounds, whereas mir-21 showed more variability. Moreover, similar data were obtained in two different laboratories, underlining the reproducibility and technical transferability of the results, a key requirement for the implementation of novel biomarkers. In conclusion, the selected miRNAs behaved like sensitive biomarkers of damage to tubular epithelial cells caused by several nephrotoxicity mechanisms. This biomarker panel, in combination with the 3D cultures of ciPTEC-OAT1 in the OrganoPlate, represents a novel tool for in vitro nephrotoxicity detection. These results pave the way for the application of miRNAs in longitudinal, time-course in vitro toxicity studies.
dc.description.urihttps://www.ncbi.nlm.nih.gov/pubmed/30039346
dc.description.urihttps://link.springer.com/article/10.1208%2Fs12248-018-0245-2
dc.language.isoen
dc.relation.ispartofThe APPS Journal (An official Journal of the American Association of Pharmaceutical Scientists)
dc.accessRightsAnonymous
dc.subjectbiomarker
dc.subjectkidney
dc.subjectmicrofluidics
dc.subjectmiRNA
dc.subjectnephrotoxiciy
dc.subjectorgan-on-a-chip
dc.titleCombining Extracellular miRNA Determination with Microfluidic 3D Cell Cultures for the Assessment of Nephrotoxicity: a Proof of Concept Study
dc.type01 - Zeitschriftenartikel, Journalartikel oder Magazin
dc.volume2018
dc.issue20
dc.audienceScience
fhnw.publicationStatePublished
fhnw.ReviewTypeAnonymous ex ante peer review of a complete publication
fhnw.InventedHereYes
fhnw.PublishedSwitzerlandNo
fhnw.IsStudentsWorkno
fhnw.publicationOnlineJa


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