Suter-Dick, Laura

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Suter-Dick
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Laura
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Suter-Dick, Laura

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2018 - 201912020 - 20211
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Autor:in: Masereeuw, Rosalinde × Typ: 01A - Beitrag in wissenschaftlicher Zeitschrift ×

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    Publikation
    Nephroscreen. A robust and versatile renal tubule-on-a-chip platform for nephrotoxicity assessment
    (Elsevier, 03/2021) Suter-Dick, Laura; Vriend, Jelle; Vormann, Marianne; Lanz, Henriette; Joore, Jos; Trietsch, Sebastian J.; Russel, Frans; Jacobsen, Björn; Roth, Adrian; Lu, Shuyan; Polli, Joseph; Naidoo, Anita; Masereeuw, Rosalinde; Wilmer, Martijn [in: Current Opinion in Toxicology]
    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.
    01A - Beitrag in wissenschaftlicher Zeitschrift
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    Publikation
    Combining Extracellular miRNA Determination with Microfluidic 3D Cell Cultures for the Assessment of Nephrotoxicity: a Proof of Concept Study
    (07/2018) Suter-Dick, Laura; Mauch, Linda; Ramp, Daniela; Caj, Michaela; Vormann, Marianne K.; Hutter, Simon; Lanz, Henriette; Vriend, Jelle; Masereeuw, Rosalinde; Wilmer, Martijn [in: The AAPS Journal]
    Drug-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.
    01A - Beitrag in wissenschaftlicher Zeitschrift