ArticleScientific reports2019
Effective reconstruction of functional organotypic kidney spheroid for in vitro nephrotoxicity studies.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 27 citations in OpenAlex.
- Beyond monolayers: a comparative analysis of 2D cell cultures and 3DFrontiers in bioengineering and biotechnology · 2026Review
- New Dimensions in Diabetic Kidney Disease Research: Advanced Organoids and Organs-on-a-Chip.BME frontiers · 2026Review
- Unveiling spontaneous renal tubule-like structures from human adult renal progenitor cell spheroids derived from urine.Stem cells translational medicine · 2025Article
- Review
- Advanced Kidney Models In Vitro Using the Established Cell Line Renal Proximal Tubular Epithelial/Telomerase Reverse Transcriptase1 for Nephrotoxicity Assays.Biomimetics (Basel, Switzerland) · 2024Article
- Kidney Disease Modeling with Organoids and Organs-on-Chips.Annual review of biomedical engineering · 2024Review
- Enhancing maturity in 3D kidney micro-tissues through clonogenic cell combinations and endothelial integration.Journal of cellular and molecular medicine · 2024Article
- Guidelines for Manufacturing and Application of Organoids: Kidney.International journal of stem cells · 2024Article
- Porcine Kidney Organoids Derived from Naïve-like Embryonic Stem Cells.International journal of molecular sciences · 2024Article
- HK-2 cell response to TGF-β highly depends on cell culture medium formulations.Histochemistry and cell biology · 2024Article
- A comprehensive review on 3D tissue models: Biofabrication technologies and preclinical applications.Biomaterials · 2024Review
- Plant vs. Kidney: Evaluating Nephrotoxicity of Botanicals with the Latest Toxicological Tools.Current opinion in toxicology · 2022Article
- Experimental models of acute kidney injury for translational research.Nature reviews. Nephrology · 2022Review
- Drug toxicity in the proximal tubule: new models, methods and mechanisms.Pediatric nephrology (Berlin, Germany) · 2022Review
- Calcium-Sensing Receptors Control CYP27B1-Luciferase Expression: Transcriptional and Posttranscriptional Mechanisms.Journal of the Endocrine Society · 2021Article
- Mechanism and reversal of drug-induced nephrotoxicity on a chip.Science translational medicine · 2021Article
- Clinostat 3D Cell Culture: Protocols for the Preparation and Functional Analysis of Highly Reproducible, Large, Uniform Spheroids and Organoids.Methods in molecular biology (Clifton, N.J.) · 2021Article
- 3-D Human Renal Tubular Organoids Generated from Urine-Derived Stem Cells for Nephrotoxicity Screening.ACS biomaterials science & engineering · 2020Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Stable and reproducible kidney cellular models could accelerate our understanding of diseases, help therapeutics development, and improve nephrotoxicity screenings. Generation of a reproducible in vitro kidney models has been challenging owing to the cellular heterogeneity and structural complexity of the kidney. We generated mixed immortalized cell lines that stably maintained their characteristic expression of renal epithelial progenitor markers for the different lineages of kidney cellular compartments via the BMP7 signaling pathway from a mouse and a human whole kidney. These cells were used to generate functional and matured kidney spheroids containing multiple renal lineages, such as the proximal tubule, loop of Henle, distal tubules, and podocytes, using extracellular matrix and physiological force, named spheroid-forming unit (SFU). They expressed all apical and basolateral transporters that are important for drug metabolism and displayed key functional aspects of the proximal tubule, including protein endocytosis and increased gamma-glutamyltransferase activity, and cyclic AMP responded to external cues, such as parathyroid hormone. Following exposure, cells fluxed and took up drugs via proximal tubule-specific apical or basolateral transporters, and displayed increased cell death and expression of renal injury marker. Here, we developed a new differentiation method to generate kidney spheroids that structurally recapitulate important features of the kidney effectively and reproducibly using mixed immortalized renal cells, and showed their application for renal toxicity studies.
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