ArticleToxicology in vitro : an international journal published in association with BIBRA2019
Characterisation of a functional rat hepatocyte spheroid model.
Article in Toxicology in vitro : an international journal published in association with BIBRA, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
17 citing papers in PubMed, 40 citations in OpenAlex.
- The effect of rocking speed and cell inoculation density on hepatic spheroid size: A simple method for size modulation.Bioengineering & translational medicine · 2026Article
- Imaging 3D cell cultures with optical microscopy.Nature methods · 2025Review
- Article
- Comparison of Engineered Liver 3D Models and the Role of Oxygenation for Patient-Derived Tumor Cells and Immortalized Cell Lines Cocultured with Tumor Stroma in the Detection of Hepatotoxins.Advanced biology · 2024Article
- Comparative Evaluation of the Cytotoxicity of Doxorubicin in BT-20 Triple-Negative Breast Carcinoma Monolayer and Spheroid Cultures.Biomedicines · 2023Article
- Spheroid Culture System, a Promising Method for Chondrogenic Differentiation of Dental Mesenchymal Stem Cells.Biomedicines · 2023Article
- A hepatoprotective role of peritumoral non-parenchymal cells in early liver tumorigenesis.Disease models & mechanisms · 2023Article
- Three-Dimensional Spheroids for Cancer Research.Methods in molecular biology (Clifton, N.J.) · 2023Article
- 3D bioprinting of dECM-incorporated hepatocyte spheroid for simultaneous promotion of cell-cell and -ECM interactions.Frontiers in bioengineering and biotechnology · 2023Article
- Current strategies with implementation of three-dimensional cell culture: the challenge of quantification.Interface focus · 2022Review
- 3D Spheroids of Human Primary Urine-Derived Stem Cells in the Assessment of Drug-Induced Mitochondrial Toxicity.Pharmaceutics · 2022Article
- Transplantation of 3D adipose-derived stem cell/hepatocyte spheroids alleviates chronic hepatic damage in a rat model of thioacetamide-induced liver cirrhosis.Scientific reports · 2022Article
- Engineering Modular 3D Liver Culture MicroenvironmentsAdvanced nanobiomed research · 2022Article
- Modular assembly-based approach of loosely packing co-cultured hepatic tissue elements with endothelialization for liver tissue engineering.Annals of translational medicine · 2020Article
- Multiscale modelling of drug transport and metabolism in liver spheroids.Interface focus · 2020Article
- Preparation of Primary Rat Hepatocyte Spheroids Utilizing the Liquid-Overlay Technique.Current protocols in toxicology · 2019Article
- Comprehensive Evaluation of Organotypic and Microphysiological Liver Models for Prediction of Drug-Induced Liver Injury.Frontiers in pharmacology · 2019Review
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 1 country.
Funding
Abstract
Many in vitro liver cell models, such as 2D systems, that are used to assess the hepatotoxic potential of xenobiotics suffer major limitations arising from a lack of preservation of physiological phenotype and metabolic competence. To circumvent some of these limitations there has been increased focus on producing more representative 3D models. Here we have used a novel approach to construct a size-controllable 3D hepatic spheroid model using freshly isolated primary rat hepatocytes (PRH) utilising the liquid-overlay technique whereby PRH spontaneously self-assemble in to 3D microtissues. This system produces viable spheroids with a compact in vivo-like structure for up to 21 days with sustained albumin production for the duration of the culture period. F-actin was seen throughout the spheroid body and P-glycoprotein (P-gp) and multidrug resistance-associated protein 2 (MRP2) transporters had polarised expression on the canalicular membrane of hepatocytes within the spheroids upon formation (day 3). The MRP2 transporter was able to functionally transport 5 μM 5-chloromethylfluorescein diacetate (CMFDA) substrates into these canalicular structures. These PRH spheroids display in vivo characteristics including direct cell-cell contacts, cellular polarisation, 3D cellular morphology, and formation of functional secondary structures throughout the spheroid. Such a well-characterised system could be readily exploited for pre-clinical and non-clinical repeat-dose investigations and could make a significant contribution to replace, reduce and refine the use of animals for applied research.
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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.