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

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.

SUBMITTER: Azuma H 

PROVIDER: S-EPMC3404624 | biostudies-literature | 2007 Aug

REPOSITORIES: biostudies-literature