Format

Send to

Choose Destination
Nat Biotechnol. 2007 Aug;25(8):903-10. Epub 2007 Jul 29.

Robust expansion of human hepatocytes in Fah-/-/Rag2-/-/Il2rg-/- mice.

Author information

1
Oregon Stem Cell Center, Oregon Health & Science University, Portland, Oregon 97239, USA.

Abstract

Mice that could be highly repopulated with human hepatocytes would have many potential uses in drug development and research applications. The best available model of liver humanization, the uroplasminogen-activator transgenic model, has major practical limitations. To provide a broadly useful hepatic xenorepopulation system, we generated severely immunodeficient, fumarylacetoacetate hydrolase (Fah)-deficient mice. After pretreatment with a urokinase-expressing adenovirus, these animals could be highly engrafted (up to 90%) with human hepatocytes from multiple sources, including liver biopsies. Furthermore, human cells could be serially transplanted from primary donors and repopulate the liver for at least four sequential rounds. The expanded cells displayed typical human drug metabolism. This system provides a robust platform to produce high-quality human hepatocytes for tissue culture. It may also be useful for testing the toxicity of drug metabolites and for evaluating pathogens dependent on human liver cells for replication.

Comment in

PMID:
17664939
PMCID:
PMC3404624
DOI:
10.1038/nbt1326
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center