ArticleScientific reports2016
Cell biology is different in small volumes: endogenous signals shape phenotype of primary hepatocytes cultured in microfluidic channels.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
35 citing papers in PubMed.
- Mechanical stiffness orchestrates distinct regulation of MRTFs and YAP/TAZ transcriptional cofactors in hepatocytes.The FEBS journal · 2026Article
- Review
- Microfluidic Modeling of Macrophage-Induced Cardiac Inflammation Using NF-κB Reporter Cardiomyocytes.Advanced healthcare materials · 2026Article
- Human Organoids and Organ-on-Chip for Biotoxin Assessment: Applications, Best Practices, and a Translational Roadmap.Toxins · 2026Review
- Scaling human liver microphysiological systems: implementing a higher-throughput liver acinus microphysiological system platform.Experimental biology and medicine (Maywood, N.J.) · 2026Article
- Vitrification and rapid rewarming of precision-cut liver slices for pharmacological and biomedical research.Bioengineering & translational medicine · 2026Article
- Article
- Enhanced PDMS Functionalization for Organ-on-a-Chip Platforms Using Ozone and Sulfo-SANPAH: A Simple Approach for Biomimetic Long-Term Cell Cultures.Advanced healthcare materials · 2025Article
- Advanced In Vitro Models for Preclinical Drug Safety: Recent Progress and Prospects.Current issues in molecular biology · 2024Review
- Liver-on-chips for drug discovery and development.Materials today. Bio · 2024Review
- 3D stem-like spheroids-on-a-chip for personalized combinatorial drug testing in oral cancer.Journal of nanobiotechnology · 2024Article
- Microfluidic 3D hepatic cultures integrated with a droplet-based bioanalysis unit.Biosensors & bioelectronics · 2024Article
- Function of hepatocyte spheroids in bioactive microcapsules is enhanced by endogenous and exogenous hepatocyte growth factor.Bioactive materials · 2023Article
- Modeling Gut Neuro-Epithelial Connections in a Novel Micro uidic Device.Research square · 2023Article
- Article
- Review
- A Microfluidic Device for Long-Term Maintenance of Organotypic Liver Cultures.Advanced materials technologies · 2023Article
- Modeling gut neuro-epithelial connections in a novel microfluidic device.Microsystems & nanoengineering · 2023Article
- Multiplexed microfluidic chip for cell co-culture.The Analyst · 2022Article
- Hepatocyte cultures: From collagen gel sandwiches to microfluidic devices with integrated biosensors.APL bioengineering · 2021Review
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
The approaches for maintaining hepatocytes in vitro are aimed at recapitulating aspects of the native liver microenvironment through the use of co-cultures, surface coatings and 3D spheroids. This study highlights the effects of spatial confinement-a less studied component of the in vivo microenvironment. We demonstrate that hepatocytes cultured in low-volume microfluidic channels (microchambers) retain differentiated hepatic phenotype for 21 days whereas cells cultured in regular culture plates under identical conditions de-differentiate after 7 days. Careful consideration of nutrient delivery and oxygen tension suggested that these factors could not solely account for enhanced cell function in microchambers. Through a series of experiments involving microfluidic chambers of various heights and inhibition of key molecular pathways, we confirmed that phenotype of hepatocytes in small volumes was shaped by endogenous signals, both hepato-inductive growth factors (GFs) such as hepatocyte growth factor (HGF) and hepato-disruptive GFs such as transforming growth factor (TGF)-β1. Hepatocytes are not generally thought of as significant producers of GFs-this role is typically assigned to nonparenchymal cells of the liver. Our study demonstrates that, in an appropriate microenvironment, hepatocytes produce hepato-inductive and pro-fibrogenic signals at the levels sufficient to shape their phenotype and function.
Identifiers
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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.