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Sci Rep. 2016 Feb 26;6:22154. doi: 10.1038/srep22154.

Generation and characterization of rat liver stem cell lines and their engraftment in a rat model of liver failure.

Author information

1
Hubrecht Institute, KNAW and University Medical Center Utrecht, 3584CT Utrecht, The Netherlands.
2
University Medical Center Utrecht, PO Box 85060, 3508 AB Utrecht, The Netherlands.
3
Department of Physiology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
4
Wellcome Trust/MRC Stem Cell Institute, Department of Physiology, Development and Neuroscience, University of Cambridge, Tennis Court Rd, Cambridge CB2 1QN, UK.
5
Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Rd, Cambridge CB2 1QN, UK.
6
Human and Molecular Genetics Center, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, 53226, WI, USA.

Abstract

The rat is an important model for liver regeneration. However, there is no in vitro culture system that can capture the massive proliferation that can be observed after partial hepatectomy in rats. We here describe the generation of rat liver stem cell lines. Rat liver stem cells, which grow as cystic organoids, were characterized by high expression of the stem cell marker Lgr5, by the expression of liver progenitor and duct markers, and by low expression of hepatocyte markers, oval cell markers, and stellate cell markers. Prolonged cultures of rat liver organoids depended on high levels of WNT-signalling and the inhibition of BMP-signaling. Upon transplantation of clonal lines to a Fah(-/-) Il2rg(-/-) rat model of liver failure, the rat liver stem cells engrafted into the host liver where they differentiated into areas with FAH and Albumin positive hepatocytes. Rat liver stem cell lines hold potential as consistent reliable cell sources for pharmacological, toxicological or metabolic studies. In addition, rat liver stem cell lines may contribute to the development of regenerative medicine in liver disease. To our knowledge, the here described liver stem cell lines represent the first organoid culture system in the rat.

PMID:
26915950
PMCID:
PMC4768167
DOI:
10.1038/srep22154
[Indexed for MEDLINE]
Free PMC Article

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