ArticleScientific reports2021
Generation of proliferating human adult hepatocytes using optimized 3D culture conditions.
Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 54 citations in OpenAlex.
- Review
- The Latest Therapeutic Targets and New Drug Research of Metabolic Dysfunction-Associated Steatotic Liver Disease.Clinical pharmacology and therapeutics · 2026Review
- Metabolic dysfunction‑associated steatotic liver disease: Pathogenesis, model and treatment (Review).International journal of molecular medicine · 2025Review
- High-yield isolation of primary human hepatocytes from small liver samples.In vitro models · 2025Article
- Rotating culture regulates the formation of HepaRG-derived liver organoids via YAP translocation.BMC biology · 2024Article
- Chronotoxici-Plate Containing Droplet-Engineered Rhythmic Liver Organoids for Drug Toxicity Evaluation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Effect of Valproic Acid on Promoting the Differentiation of Human Embryonic Stem Cells Into Cholangiocyte-Like Cells.Stem cells translational medicine · 2024Article
- The ENDOMIX project: an interdisciplinary approach to understanding how real-life chemical mixtures target the immune system to trigger disease.Open research Europe · 2024Article
- Direct mechanical exposure initiates hepatocyte proliferation.JHEP reports : innovation in hepatology · 2023Article
- Organoid Establishment of Long-Term Culture Using Primary Mouse Hepatocytes and Evaluation of Liver Function.Preventive nutrition and food science · 2023Article
- Engineered human liver based on pullulan-dextran hydrogel promotes mice survival after liver failure.Materials today. Bio · 2023Article
- High-throughput micronucleus assay using three-dimensional HepaRG spheroids for in vitro genotoxicity testing.Archives of toxicology · 2023Article
- Recent advances in liver-on-chips: Design, fabrication, and applications.Smart medicine · 2023Review
- Primary Hepatocyte Isolation and Cultures: Technical Aspects, Challenges and Advancements.Bioengineering (Basel, Switzerland) · 2023Review
- Three-dimensional human bile duct formation from chemically induced human liver progenitor cells.Frontiers in bioengineering and biotechnology · 2023Article
- Long-Term Characteristics of Human-Derived Biliary Organoids under a Single Continuous Culture Condition.Cells · 2022Article
- Optimization of 3D-aggregated spheroid model (3D-ASM) for selecting high efficacy drugs.Scientific reports · 2022Article
- Isolation of Hepatocytes from Liver Tissue by a Novel, Semi-Automated Perfusion Technology.Biomedicines · 2022Article
- Article
- In vitro proliferation and long-term preservation of functional primary rat hepatocytes in cell fibers.Scientific reports · 2022Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Generating the proliferation of differentiated normal adult human hepatocytes is a major challenge and an expected central step in understanding the microenvironmental conditions that regulate the phenotype of human hepatocytes in vitro. In this work, we described optimized 3D culture conditions of primary human hepatocytes (PHH) to trigger two waves of proliferation and we identified matrix stiffness and cell-cell interactions as the main actors necessary for this proliferation. We demonstrated that DNA replication and overexpression of cell cycle markers are modulate by the matrix stiffness while PHH cultured in 3D without prior cellular interactions did not proliferate. Besides, we showed that PHH carry out an additional cell cycle after transient inhibition of MAPK MER1/2-ERK1/2 signaling pathway. Collagen cultured hepatocytes are organized as characteristic hollow spheroids able to maintain survival, cell polarity and hepatic differentiation for long-term culture periods of at least 28 days. Remarkably, we demonstrated by transcriptomic analysis and functional experiments that proliferating cells are mature hepatocytes with high detoxication capacities. In conclusion, the advanced 3D model described here, named Hepoid, is particularly relevant for obtaining normal human proliferating hepatocytes. By allowing concomitant proliferation and differentiation, it constitutes a promising tool for many pharmacological and biotechnological 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.