Generation of Hepatocyte-Like Cells from Human Embryonic Stem Cells
Open accessAbstract
Use of human hepatocytes for therapeutic and drug discovery applications is hampered by limited tissue source and the inability of hepatocytes to proliferate and maintain function long term in vitro. Human embryonic stem (hES) cells are immortal and pluripotent and may provide a cell source for functional human hepatocytes. We report here that hES cells can be induced to differentiate into hepatocyte-like cells. Treatment with sodium butyrate induced hepatic differentiation as well as significant cell death, resulting in approximately 10–15% yield of a homogeneous population of cells. The differentiated cells have morphological features similar to that of primary hepatocytes and 70–80% of the cells express liver-associated proteins (albumin, alpha-1-antitrypsin, cytokeratin 8 and 18), accumulate glycogen, have inducible cytochrome P450 activity, and do not express alpha-fetoprotein. Because of the inherent proliferative capacity of hES cells, these cells may provide a reliable source of normal human hepatocytes for research and transplantation.
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Simple in vitro culture systems may support similar expression patterns during both hepatic dedifferentiation and differentiation, because proteins up-regulated in dedifferentiation are readily detectable in stem cell-derived hepatocyte-like cells whereas many down-regulated proteins are not.
“Interestingly, these proteins are readily detectable in hepatocyte-like cells derived from stem cells (Rambhatla et al. 2003), whereas many of the down-regulated proteins are not, demonstrating that simple in vitro culture systems may support similar expression patterns during both hepatic dedifferentiation and differentiation.”
From Mechanistic evaluation of primary human hepatocyte culture using global proteomic analysis reveals a selective dedifferentiation profile (2017) · cites this paper as Rambhatla et al. 2003
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References 34 · Cited by 437
- Authors
- Rambhatla, L., Chiu, C.-P., Kundu, P., Peng, Y., & Carpenter, M. K.
- Affiliations
- Geron (United States) (US)
- Corresponding author
- Carpenter, Melissa K.
- Venue
- Cell Transplantation
- Publisher
- SAGE Publications
- Published
- 2003-01
- Volume
- 12
- Issue
- 1
- Pages
- 1-11
- ISSN
- 0963-6897 (ISSN-L)
- 1555-3892
- OpenAlex
- W1970023965
- Cited by
- 437
- References
- 34
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 3 · 2023: 5 · 2022: 8 · 2021: 9 · 2020: 11 · 2019: 5 · 2018: 8 · 2017: 5 · 2016: 7 · 2015: 9 · 2014: 17 · 2013: 18 · 2012: 30
- FWCI
- 14.48
- Type
- journal article
- Language
- en
- Open access
- green
- doaj.org
- Locations
- Cell Transplantation (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- human embryonic stem cells, hepatocyte-like cells, hepatocyte differentiation, sodium butyrate, liver regeneration, hepatocyte transplantation, drug discovery, cytochrome P450, glycogen accumulation, alpha-1-antitrypsin, albumin, alpha-fetoprotein
- MeSH terms
- Adult, alpha-Fetoproteins, Butyrates, Cell Differentiation, Cells, Cultured, Cytochrome P-450 Enzyme System, Fetus, Glycogen, Humans, Hydroxamic Acids, Protein Synthesis Inhibitors, Biomarkers, Gene Expression, Cell Death, Cell Culture Techniques, Hepatocytes, Stem Cell Transplantation, Pluripotent Stem Cells, Cell Size
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