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Hepatocyte-like cells derived from human embryonic stem cells specifically via definitive endoderm and a progenitor stage

Paper ID Volume ID Publish Year Pages File Format Full-Text
24484 43518 2010 11 PDF Available
Title
Hepatocyte-like cells derived from human embryonic stem cells specifically via definitive endoderm and a progenitor stage
Abstract

Human embryonic stem cells offer a potential unlimited supply for functional hepatocytes, since they can differentiate into hepatocyte-like cells displaying a characteristic hepatic morphology and expressing various hepatic markers. These cells could be used in various applications such as studies of drug metabolism and hepatotoxicity, which however, would require a significant expression of drug metabolizing enzymes. To derive these cells we use a stepwise differentiation protocol where growth- and maturation factors are added. The first phase involves the formation of definitive endoderm. Next, these cells are treated with factors known to promote the induction and proliferation towards hepatic progenitor cell types. In the last phase the cells are terminally differentiated and maturated into functional hepatocyte-like cells. The cultures were characterized by analysis of endodermal or hepatic markers and compared to cultures derived without induction via definitive endoderm. Hepatic functions such as urea secretion, glycogen storage, indocyanine green uptake and secretion, and cytochrome P450-expression and activity were evaluated.The DE-Hep showed a hepatocyte morphology with sub-organized cells and exhibited many liver-functions including transporter activity and capacity to metabolize drugs specific for important cytochrome P450 sub-families. This represents an important step in differentiation of hESC into functional hepatocytes.

Keywords
Human embryonic stem cell; Definitive endoderm; Hepatocyte; Liver progenitor; Activin
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Hepatocyte-like cells derived from human embryonic stem cells specifically via definitive endoderm and a progenitor stage
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Publisher
Database: Elsevier - ScienceDirect
Journal: Journal of Biotechnology - Volume 145, Issue 3, 1 February 2010, Pages 284–294
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us