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

Brolen, Gabriella; Sivertsson, Louise; Bjorquist, Petter; Eriksson, Gustav; Ek, Monica; Semb, Henrik LU ; Johansson, Inger; Andersson, Tommy B.; Ingelman-Sundberg, Magnus and Heins, Nico (2010) In Journal of Biotechnology 145(3). p.284-294
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... (More)
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 importantstep in differentiation of hESC into functional hepatocytes. (C) 2009 Elsevier B.V. All rights reserved. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Liver, Hepatocyte, Human embryonic stem cell, Definitive endoderm, progenitor, Activin
in
Journal of Biotechnology
volume
145
issue
3
pages
284 - 294
publisher
Elsevier
external identifiers
  • wos:000274926200011
  • scopus:74149094915
ISSN
1873-4863
DOI
10.1016/j.jbiotec.2009.11.007
language
English
LU publication?
yes
id
9a579750-8d30-43e4-b6d6-f8267e2ee4a9 (old id 1568139)
date added to LUP
2010-03-23 14:34:45
date last changed
2018-05-29 10:32:51
@article{9a579750-8d30-43e4-b6d6-f8267e2ee4a9,
  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 importantstep in differentiation of hESC into functional hepatocytes. (C) 2009 Elsevier B.V. All rights reserved.},
  author       = {Brolen, Gabriella and Sivertsson, Louise and Bjorquist, Petter and Eriksson, Gustav and Ek, Monica and Semb, Henrik and Johansson, Inger and Andersson, Tommy B. and Ingelman-Sundberg, Magnus and Heins, Nico},
  issn         = {1873-4863},
  keyword      = {Liver,Hepatocyte,Human embryonic stem cell,Definitive endoderm,progenitor,Activin},
  language     = {eng},
  number       = {3},
  pages        = {284--294},
  publisher    = {Elsevier},
  series       = {Journal of Biotechnology},
  title        = {Hepatocyte-like cells derived from human embryonic stem cells specifically via definitive endoderm and a progenitor stage},
  url          = {http://dx.doi.org/10.1016/j.jbiotec.2009.11.007},
  volume       = {145},
  year         = {2010},
}