The DOI matches its Crossref record; 33 of the 33 references it cites were found in a registry or an index.
Differentiation and Transplantation of Human Embryonic Stem Cell–Derived Hepatocytes
Open accessAbstract
Background & Aims The ability to obtain unlimited numbers of human hepatocytes would improve 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, can potentially differentiate into any cell type and could therefore be developed as a source of human hepatocytes. Methods To 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 PCR, imunohistochemistry, immunoblot, functional assays and transplantation. Results Embryonic 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 demonstrated human hepatocyte cytochrome P450 metabolic activity. Serum from rodents given injections of embryonic stem cell-derived hepatocytes contained significant amounts of human albumin and alpha-1-antitrypsin. Colonies of cytokeratin-18 and human albumin-expressing cells were present in the livers of recipient animals. Conclusion Human 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 could potentially be used in drug discovery research and developed as therapeutics.
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Cited by
Directed differentiation of human pluripotent stem cells into intestinal tissue in vitro
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Stem Cells and Liver Regeneration
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Metadata
- Authors
- Basma, H., Soto–Gutiérrez, A., Yannam, G. R., Liu, L., Ito, R., Yamamoto, T., Ellis, E., Carson, S. D., Sato, S., Chen, Y., Muirhead, D., Navarro–Álvarez, N., Wong, R. J., Roy–Chowdhury, J., Platt, J. L., Mercer, D. F., Miller, J. D., Strom, S. C., Kobayashi, N., & Fox, I. J.
- Venue
- Gastroenterology
- Publisher
- Elsevier BV
- Published
- 2009-03
- Volume
- 136
- Issue
- 3
- Pages
- 990-999.e4
- ISSN
- 0016-5085 (ISSN-L)
- OpenAlex
- W2094689158
- Cited by
- 516
- References
- 33
- FWCI
- 16.38
- Type
- journal article
- Language
- en
- Open access
- green
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- Basma, H., Soto–Gutiérrez, A., Yannam, G. R., Liu, L., Ito, R., Yamamoto, T., Ellis, E., Carson, S. D., Sato, S., Chen, Y., Muirhead, D., Navarro–Álvarez, N., Wong, R. J., Roy–Chowdhury, J., Platt, J. L., Mercer, D. F., Miller, J. D., Strom, S. C., Kobayashi, N., & Fox, I. J. (2009). Differentiation and Transplantation of Human Embryonic Stem Cell–Derived Hepatocytes. Gastroenterology. https://doi.org/10.1053/j.gastro.2008.10.047
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