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

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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; Johansson, Inger; Andersson, Tommy B.; Ingelman-Sundberg, Magnus; Heins, Nico.

In: Journal of Biotechnology, Vol. 145, No. 3, 2010, p. 284-294.

Research output: Contribution to journalArticle

Harvard

Brolen, G, Sivertsson, L, Bjorquist, P, Eriksson, G, Ek, M, Semb, H, Johansson, I, Andersson, TB, Ingelman-Sundberg, M & Heins, N 2010, 'Hepatocyte-like cells derived from human embryonic stem cells specifically via definitive endoderm and a progenitor stage', Journal of Biotechnology, vol. 145, no. 3, pp. 284-294. https://doi.org/10.1016/j.jbiotec.2009.11.007

APA

CBE

Brolen G, Sivertsson L, Bjorquist P, Eriksson G, Ek M, Semb H, Johansson I, Andersson TB, Ingelman-Sundberg M, Heins N. 2010. Hepatocyte-like cells derived from human embryonic stem cells specifically via definitive endoderm and a progenitor stage. Journal of Biotechnology. 145(3):284-294. https://doi.org/10.1016/j.jbiotec.2009.11.007

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Author

Brolen, Gabriella ; Sivertsson, Louise ; Bjorquist, Petter ; Eriksson, Gustav ; Ek, Monica ; Semb, Henrik ; Johansson, Inger ; Andersson, Tommy B. ; Ingelman-Sundberg, Magnus ; Heins, Nico. / Hepatocyte-like cells derived from human embryonic stem cells specifically via definitive endoderm and a progenitor stage. In: Journal of Biotechnology. 2010 ; Vol. 145, No. 3. pp. 284-294.

RIS

TY - JOUR

T1 - Hepatocyte-like cells derived from human embryonic stem cells specifically via definitive endoderm and a progenitor stage

AU - Brolen, Gabriella

AU - Sivertsson, Louise

AU - Bjorquist, Petter

AU - Eriksson, Gustav

AU - Ek, Monica

AU - Semb, Henrik

AU - Johansson, Inger

AU - Andersson, Tommy B.

AU - Ingelman-Sundberg, Magnus

AU - Heins, Nico

N1 - The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Stem Cell and Pancreas Developmental Biology (013212044)

PY - 2010

Y1 - 2010

N2 - 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.

AB - 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.

KW - Liver

KW - Hepatocyte

KW - Human embryonic stem cell

KW - Definitive endoderm

KW - progenitor

KW - Activin

U2 - 10.1016/j.jbiotec.2009.11.007

DO - 10.1016/j.jbiotec.2009.11.007

M3 - Article

VL - 145

SP - 284

EP - 294

JO - Journal of Biotechnology

T2 - Journal of Biotechnology

JF - Journal of Biotechnology

SN - 1873-4863

IS - 3

ER -