The DOI matches its Crossref record; 67 of the 67 references it cites were found in a registry or an index.
Efficient Differentiation of Functional Hepatocytes from Human Embryonic Stem Cells
Abstract
Differentiation of human embryonic stem cells (hESCs) to specific functional cell types can be achieved using methods that mimic in vivo embryonic developmental programs. Current protocols for generating hepatocytes from hESCs are hampered by inefficient differentiation procedures that lead to low yields and large cellular heterogeneity. We report here a robust and highly efficient process for the generation of high-purity (70%) hepatocyte cultures from hESCs that parallels sequential hepatic development in vivo. Highly enriched populations of definitive endoderm were generated from hESCs and then induced to differentiate along the hepatic lineage by the sequential addition of inducing factors implicated in physiological hepatogenesis. The differentiation process was largely uniform, with cell cultures progressively expressing increasing numbers of hepatic lineage markers, including GATA4, HNF4α, α-fetoprotein, CD26, albumin, α-1-antitrypsin, Cyp7A1, and Cyp3A4. The hepatocytes exhibited functional hepatic characteristics, such as glycogen storage, indocyanine green uptake and release, and albumin secretion. In a mouse model of acute liver injury, the hESC-derived definitive endoderm differentiated into hepatocytes and repopulated the damaged liver. The methodology described here represents a significant step toward the efficient generation of hepatocytes for use in regenerative medicine and drug discovery. Disclosure of potential conflicts of interest is found at the end of this article.
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Cites
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Development of definitive endoderm from embryonic stem cells in culture
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Oct‐4 : Gatekeeper in the Beginnings of Mammalian Development
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Depletion of definitive gut endoderm in Sox17 -null mutant mice
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Cited by
Highly efficient generation of human hepatocyte-like cells from induced pluripotent stem cells
Si-Tayeb, K., Noto, F. K., Nagaoka, M., Li, J., Battle, M. A., Duris, C., North, P. E., Dalton, S., & Duncan, S. A. (2010) · Hepatology · doi:10.1002/hep.23354 · Cited by 1,282
Godoy, P., Hewitt, N. J., Albrecht, U., Andersen, M. E., Ansari, N., Bhattacharya, S., Bode, J. G., Bolleyn, J., Borner, C., Böttger, J., et al. (2013) · Archives of Toxicology · doi:10.1007/s00204-013-1078-5 · Cited by 1,280
In vitro models for liver toxicity testing
Soldatow, V. Y., LeCluyse, E. L., Griffith, L. G., & Rusyn, I. (2013) · Toxicol. Res. · doi:10.1039/c2tx20051a · Cited by 472
Organotypic liver culture models: meeting current challenges in toxicity testing
LeCluyse, E. L., Witek, R. P., Andersen, M. E., & Powers, M. J. (2012) · Critical Reviews in Toxicology · doi:10.3109/10408444.2012.682115 · Cited by 363
Cell and tissue engineering for liver disease
Bhatia, S. N., Underhill, G. H., Zaret, K. S., & Fox, I. J. (2014) · Science Translational Medicine · doi:10.1126/scitranslmed.3005975 · Cited by 309
Metadata
- Authors
- Agarwal, S., Holton, K. L., & Lanza, R.
- Venue
- Stem Cells
- Publisher
- Oxford University Press (OUP)
- Published
- 2008-02-21
- Volume
- 26
- Issue
- 5
- Pages
- 1117-1127
- ISSN
- 1066-5099 (ISSN-L)
- 1549-4918
- OpenAlex
- W2034745491
- Cited by
- 405
- References
- 67
- FWCI
- 15.51
- Type
- journal article
- Language
- en
- Open access
- closed
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