ArticleScientific reports2019
In vitro metabolic zonation through oxygen gradient on a chip.
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 38 papers.
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Who cites it
38 citing papers in PubMed, 74 citations in OpenAlex.
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- Reverse bioengineering of the liver: developmental principles for next-generation liver-on-a-chip systems.Communications biology · 2026Review
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- Metabolic dysfunction-associated steatotic liver disease and steatohepatitis-associated hepatocarcinoma preclinical models.Nature reviews. Gastroenterology & hepatology · 2026Review
- Strategies to control cellular spatial organization in microphysiological systems.Microsystems & nanoengineering · 2026Review
- 3D Culture in Functionalized FN-Silk Networks Facilitate Proliferation, Differentiation and Phenotypic Stability of Mature Human Primary Cells and Stem Cells.Biotechnology and bioengineering · 2025Article
- Current Advances and Future Perspectives of Liver-on-a-Chip Platforms Incorporating Dynamic Fluid Flow.Biomimetics (Basel, Switzerland) · 2025Review
- hESCs-derived Organoids Achieve Liver Zonation Features through LSEC Modulation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Design, fabrication, and characterization of a user-friendly microfluidic device for studying liver zonation-on-chip (ZoC).Biomedical microdevices · 2025Article
- Computational and experimental advances in liver-on-a-chip technology for cancer research: a systematic review.Biophysical reviews · 2025Review
- 3D Bioprinting for Engineered Tissue Constructs and Patient-Specific Models: Current Progress and Prospects in Clinical Applications.Advanced materials (Deerfield Beach, Fla.) · 2024Review
- Liver-on-chips for drug discovery and development.Materials today. Bio · 2024Review
- Biofabrication methods for reconstructing extracellular matrix mimetics.Bioactive materials · 2024Review
- Fast formation and maturation enhancement of human liver organoids using a liver-organoid-on-a-chip.Frontiers in cell and developmental biology · 2024Article
- Single-cell metabolic profiling reveals subgroups of primary human hepatocytes with heterogeneous responses to drug challenge.Genome biology · 2023Article
- Distinct hepatocyte identities in liver homeostasis and regeneration.JHEP reports : innovation in hepatology · 2023Review
- Temporal Dynamics of Metabolic Acquisition in Grafted Engineered Human Liver Tissue.Advanced biology · 2023Article
- Biocompatibility of the oxygen carrier polymerized human hemoglobin towards HepG2/C3A cells.Heliyon · 2023Article
- Organs-on-a-chip: a union of tissue engineering and microfabrication.Trends in biotechnology · 2023Review
- Physiomimetic In Vitro Human Models for Viral Infection in the Liver.Seminars in liver disease · 2023Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Among the multiple metabolic signals involved in the establishment of the hepatic zonation, oxygen could play a key role. Indeed, depending on hepatocyte position in the hepatic lobule, gene expression and metabolism are differently affected by the oxygen gradient present across the lobule. The aim of this study is to understand whether an oxygen gradient, generated in vitro in our developed device, is sufficient to instruct a functional metabolic zonation during the differentiation of human embryonic stem cells (hESCs) from endoderm toward terminally differentiated hepatocytes, thus mimicking the in vivo situation. For this purpose, a microfluidic device was designed for the generation of a stable oxygen gradient. The oxygen gradient was applied to differentiating hESCs at the pre-hepatoblast stage. The definitive endoderm and hepatic endoderm cells were characterized by the expression of the transcription factor SOX-17 and alpha-fetoprotein (AFP). Immature and mature hepatocytes were characterized by hepatocyte nuclear factor 4-alpha (HNF-4α) and albumin (ALB) expression and also analyzed for cytochrome P450 (CYP3A4) zonation and glycogen accumulation through PAS staining. Metabolic zonated genes expression was assessed through quantitative real time PCR. Application of the oxygen gradient during differentiation induced zonated glycogen storage, which was higher in the hepatocytes grown in high pO
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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.