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

First Author  Azuma H Year  2007
Journal  Nat Biotechnol Volume  25
Issue  8 Pages  903-10
PubMed ID  17664939 Mgi Jnum  J:271015
Mgi Id  MGI:6188672 Doi  10.1038/nbt1326
Citation  Azuma H, et al. (2007) Robust expansion of human hepatocytes in Fah-/-/Rag2-/-/Il2rg-/- mice. Nat Biotechnol 25(8):903-10
abstractText  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.
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