ArticleThe AAPS journal2018
Combining Extracellular miRNA Determination with Microfluidic 3D Cell Cultures for the Assessment of Nephrotoxicity: a Proof of Concept Study.
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 13 papers, 3 of them syntheses that pooled it.
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Who cites it
13 citing papers in PubMed, 3 syntheses or guidelines pooled it, 40 citations in OpenAlex.
- 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
- Dysregulated MicroRNAs as Biomarkers or Therapeutic Targets in Cisplatin-Induced Nephrotoxicity: A Systematic Review.International journal of molecular sciences · 2021Pooled it
- Understanding Cisplatin Pharmacokinetics and Toxicodynamics to Predict and Prevent Kidney Injury.The Journal of pharmacology and experimental therapeutics · 2024Review
- 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
- 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
- Progress and promise of alternative animal and non-animal methods in biomedical research.Archives of toxicology · 2023Review
- Nephrotoxic antisense oligonucleotide SPC5001 induces kidney injury biomarkers in a proximal tubule-on-a-chip.Archives of toxicology · 2021Article
- Epigenetic Mechanisms Involved in Cisplatin-Induced Nephrotoxicity: An Update.Pharmaceuticals (Basel, Switzerland) · 2021Review
- A 3D Renal Proximal Tubule on Chip Model Phenocopies Lowe Syndrome and Dent II Disease Tubulopathy.International journal of molecular sciences · 2021Article
- Potential Applications of Microfluidics to Acute Kidney Injury Associated with Viral Infection.Cellular and molecular bioengineering · 2020Article
- Adding the T to ADME: Predictive Toxicity in Renal Drug Development.The AAPS journal · 2018Article
- Nephrotoxicity and Kidney Transport Assessment on 3D Perfused Proximal Tubules.The AAPS journal · 2018Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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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.