ArticleBiomaterials2014
Molecular mechanisms underlying the enhanced functions of three-dimensional hepatocyte aggregates.
Article in Biomaterials, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 54 citations in OpenAlex.
- Rotating culture regulates the formation of HepaRG-derived liver organoids via YAP translocation.BMC biology · 2024Article
- Three-Dimensional Rotary Culture to Model Mycobacterial Biofilms in Low-Shear Detergent-Free Liquid Suspension.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Structural and Molecular Changes of Human Chondrocytes Exposed to the Rotating Wall Vessel Bioreactor.Biomolecules · 2023Article
- Self-Assembled Matrigel-Free iPSC-Derived Liver Organoids Demonstrate Wide-Ranging Highly Differentiated Liver Functions.Stem cells (Dayton, Ohio) · 2023Article
- Direct lysis of 3D cell cultures for RT-qPCR gene expression quantification.Scientific reports · 2023Article
- Potential Roles of YAP/TAZ Mechanotransduction in Spaceflight-Induced Liver Dysfunction.International journal of molecular sciences · 2023Review
- Primary Hepatocyte Isolation and Cultures: Technical Aspects, Challenges and Advancements.Bioengineering (Basel, Switzerland) · 2023Review
- Hepatocyte cultures: From collagen gel sandwiches to microfluidic devices with integrated biosensors.APL bioengineering · 2021Review
- A miniature dialysis-culture device allows high-density human-induced pluripotent stem cells expansion from growth factor accumulation.Communications biology · 2021Article
- Advances in space microbiology.iScience · 2021Review
- Characterization of primary mouse hepatocyte spheroids as a model system to support investigations of drug-induced liver injury.Toxicology in vitro : an international journal published in association with BIBRA · 2021Article
- A Critical Perspective on 3D Liver Models for Drug Metabolism and Toxicology Studies.Frontiers in cell and developmental biology · 2021Review
- Dexamethasone Inhibits Spheroid Formation of Thyroid Cancer Cells Exposed to Simulated Microgravity.Cells · 2020Article
- Remodelling and Improvements in Organoid Technology to Study Liver Carcinogenesis in a Dish.Stem cells international · 2019Review
- Modeling Host-Pathogen Interactions in the Context of the Microenvironment: Three-Dimensional Cell Culture Comes of Age.Infection and immunity · 2018Review
- Detection of nanocarrier potentiation on drug induced phospholipidosis in cultured cells and primary hepatocyte spheroids by high content imaging and analysis.Toxicology and applied pharmacology · 2018Article
- Transcriptomic, Proteomic, and Functional Long-Term Characterization of Multicellular Three-Dimensional Human Liver Microtissues.Applied in vitro toxicology · 2018Article
- Three-dimensional hepatocyte culture system for the study of Echinococcus multilocularis larval development.PLoS neglected tropical diseases · 2018Article
- Direct orthotopic implantation of hepatic organoids.The Journal of surgical research · 2017Article
- Is There a Space-Based Technology Solution to Problems with Preclinical Drug Toxicity Testing?Pharmaceutical research · 2016Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Three-dimensional (3D) culture of hepatocytes leads to improved and prolonged synthetic and metabolic functions, but the underlying molecular mechanisms are unknown. In order to investigate the role of 3D cell-cell interactions in maintaining hepatocyte differentiated functions ex vivo, primary mouse hepatocytes were cultured either as monolayers on tissue culture dishes (TCD) or as 3D aggregates in rotating wall vessel (RWV) bioreactors. Global gene expression analyses revealed that genes upregulated in 3D culture were distinct from those upregulated during liver development and liver regeneration. Instead, they represented a diverse array of hepatocyte-specific functional genes with significant over-representation of hepatocyte nuclear factor 4α (Hnf4a) binding sites in their promoters. Expression of Hnf4a and many of its downstream target genes were significantly increased in RWV cultures as compared to TCD. Conversely, there was concomitant suppression of mesenchymal and cytoskeletal genes in RWV cultures that were induced in TCDs. These findings illustrate the importance of 3D cell-cell interactions in maintaining fundamental molecular pathways of hepatocyte function and serve as a basis for rational design of biomaterials that aim to optimize hepatocyte functions ex vivo for biomedical applications.
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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.