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Cited by 405

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

Agarwal, Sadhana, Holton, Katherine L., Lanza, Robert·2008·Stem Cells
DOI 10.1634/stemcells.2007-1102
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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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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
DOI
10.1634/stemcells.2007-1102
OpenAlex
W2034745491
Cited by
405
References
67
FWCI
15.51
Type
journal article
Language
en
Open access
closed

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