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

Författare:
  • Gabriella Brolen
  • Louise Sivertsson
  • Petter Bjorquist
  • Gustav Eriksson
  • Monica Ek
  • Henrik Semb
  • Inger Johansson
  • Tommy B. Andersson
  • Magnus Ingelman-Sundberg
  • Nico Heins
Publiceringsår: 2010
Språk: Engelska
Sidor: 284-294
Publikation/Tidskrift/Serie: Journal of Biotechnology
Volym: 145
Nummer: 3
Dokumenttyp: Artikel
Förlag: Elsevier Science BV

Sammanfattning

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.

Disputation

Nyckelord

  • Medicine and Health Sciences
  • Liver
  • Hepatocyte
  • Human embryonic stem cell
  • Definitive endoderm
  • progenitor
  • Activin

Övriga

Published
Yes
  • ISSN: 0168-1656

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