ArticleGastroenterology2009
Differentiation and transplantation of human embryonic stem cell-derived hepatocytes.
Article in Gastroenterology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 227 papers, 2 of them syntheses that pooled it.
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
227 citing papers in PubMed, 2 syntheses or guidelines pooled it, 515 citations in OpenAlex.
- A comprehensive transcriptomic comparison of hepatocyte model systems improves selection of models for experimental use.Communications biology · 2022Pooled it
- Guideline
- Preclinical efficacy and safety evaluation of human embryonic stem cell-derived functional hepatocytes for a clinical trial in acute liver failure.Stem cell research & therapy · 2026Article
- Mesenchymal stem cell therapy for end-stage liver disease: adversity and opportunity.Stem cell research & therapy · 2025Review
- Stem cell therapy: a novel frontier in the treatment of liver fibrosis/cirrhosis.Stem cell research & therapy · 2025Review
- Article
- Advancing hepatotoxicity assessment: current advances and future directions.Toxicological research · 2025Review
- MIXL1 activation in endoderm differentiation of human induced pluripotent stem cells.Stem cell reports · 2025Article
- Experimental Models to Investigate PNPLA3 in Liver Steatosis.Liver international : official journal of the International Association for the Study of the Liver · 2025Review
- Standard Protocols for Characterising Primary and In Vitro-Generated Human Hepatocytes.Journal of cellular and molecular medicine · 2025Review
- Classes of Stem Cells: From Biology to Engineering.Regenerative engineering and translational medicine · 2024Article
- Cis-regulatory control of transcriptional timing and noise in response to estrogen.Cell genomics · 2024Article
- Stem Cell-Based Strategies: The Future Direction of Bioartificial Liver Development.Stem cell reviews and reports · 2024Review
- Human Hepatocyte Transplantation: Three Decades of Clinical Experience and Future Perspective.Stem cells translational medicine · 2024Review
- Article
- Role of connexin 32 in the directional differentiation of induced pluripotent stem cells into hepatocytes.International journal of medical sciences · 2024Article
- Article
- Therapeutic Cell Repopulation of the Liver: From Fetal Rat Cells to Synthetic Human Tissues.Cells · 2023Review
- Development of a method of passaging and freezing human iPS cell-derived hepatocytes to improve their functions.PloS one · 2023Article
- Article
167 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
20 authors at 6 institutions in 2 countries.
Funding
Abstract
BACKGROUND &
aimsThe ability to obtain unlimited numbers of human hepatocytes would improve the development of cell-based therapies for liver diseases, facilitate the study of liver biology, and improve the early stages of drug discovery. Embryonic stem cells are pluripotent, potentially can differentiate into any cell type, and therefore could be developed as a source of human hepatocytes.
methodsTo generate human hepatocytes, human embryonic stem cells were differentiated by sequential culture in fibroblast growth factor 2 and human activin-A, hepatocyte growth factor, and dexamethasone. Functional hepatocytes were isolated by sorting for surface asialoglycoprotein-receptor expression. Characterization was performed by real-time polymerase chain reaction, immunohistochemistry, immunoblot, functional assays, and transplantation.
resultsEmbryonic stem cell-derived hepatocytes expressed liver-specific genes, but not genes representing other lineages, secreted functional human liver-specific proteins similar to those of primary human hepatocytes, and showed human hepatocyte cytochrome P450 metabolic activity. Serum from rodents given injections of embryonic stem cell-derived hepatocytes contained significant amounts of human albumin and alpha1-antitrypsin. Colonies of cytokeratin-18 and human albumin-expressing cells were present in the livers of recipient animals.
conclusionsHuman embryonic stem cells can be differentiated into cells with many characteristics of primary human hepatocytes. Hepatocyte-like cells can be enriched and recovered based on asialoglycoprotein-receptor expression and potentially could be used in drug discovery research and developed as therapeutics.
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What OpenQuestion holds
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.