Abstract

We have used mouse ES cells transfected with the green fluorescent protein (GFP) reporter gene regulated by albumin (ALB) enhancer/promoter to establish in vitro system to differentiate the ES cell into the hepatocytic lineage. We discovered that a serum-free chemically defined medium supports formation of embryoid bodies (EBs) and differentiation of hepatic lineage cells in the absence of exogenous growth factors or feeder cell layers. The FACS-purified GFP positive cells developed into functional hepatocytes without evidence of cell fusion and participated in the repairing of diseased liver when transplanted into MUP-uPA/SCID mice. We have extended this approach to human ES cell lines and are currently evaluating the efficiency of two human ES cell lines (i.e. H9 and H1) to differentiate into the hepatocytic lineage.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Intramural Research (Z01)
Project #
1Z01BC005453-24
Application #
7732879
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
24
Fiscal Year
2008
Total Cost
$280,935
Indirect Cost

  Institution

Name
National Cancer Institute Division of Basic Sciences
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

Thorgeirsson, Snorri S (2017) Stemness in Liver Cancer. Dig Dis 35:387-389
Kaji, Kosuke; Factor, Valentina M; Andersen, Jesper B et al. (2016) DNMT1 is a required genomic regulator for murine liver histogenesis and regeneration. Hepatology 64:582-98
Thorgeirsson, Snorri S; Grisham, Joe W (2006) Hematopoietic cells as hepatocyte stem cells: a critical review of the evidence. Hepatology 43:2-8
Paku, Sandor; Nagy, Peter; Kopper, Laszlo et al. (2004) 2-acetylaminofluorene dose-dependent differentiation of rat oval cells into hepatocytes: confocal and electron microscopic studies. Hepatology 39:1353-61
Sanchez, Aranzazu; Factor, Valentina M; Schroeder, Insa S et al. (2004) Activation of NF-kappaB and STAT3 in rat oval cells during 2-acetylaminofluorene/partial hepatectomy-induced liver regeneration. Hepatology 39:376-85
Terai, S; Aoki, H; Ashida, K et al. (2000) Human homologue of maid: A dominant inhibitory helix-loop-helix protein associated with liver-specific gene expression. Hepatology 32:357-66
Feng, S L; Guo, Y; Factor, V M et al. (2000) The Fn14 immediate-early response gene is induced during liver regeneration and highly expressed in both human and murine hepatocellular carcinomas. Am J Pathol 156:1253-61
Nagy, P; Bisgaard, H C; Schnur, J et al. (2000) Studies on hepatic gene expression in different liver regenerative models. Biochem Biophys Res Commun 272:591-5
Conner, E A; Teramoto, T; Wirth, P J et al. (1999) HGF-mediated apoptosis via p53/bax-independent pathway activating JNK1. Carcinogenesis 20:583-90
Bisgaard, H C; Muller, S; Nagy, P et al. (1999) Modulation of the gene network connected to interferon-gamma in liver regeneration from oval cells. Am J Pathol 155:1075-85

Showing the most recent 10 out of 12 publications