Research abstract

Article abstract

Nature Biotechnology 25, 903 - 910 (2007)
Published online: 29 July 2007 | Corrected online: 11 March 2008 | doi:10.1038/nbt1326

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

Hisaya Azuma1, Nicole Paulk1, Aarati Ranade2, Craig Dorrell1, Muhsen Al-Dhalimy1, Ewa Ellis2, Stephen Strom2, Mark A Kay3, Milton Finegold4 & Markus Grompe1

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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  1. Oregon Stem Cell Center, Oregon Health & Science University, Portland, Oregon 97239, USA.
  2. Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15261, USA.
  3. Department of Pediatrics, Stanford University, California 94305, USA.
  4. Department of Pathology, Texas Children's Hospital, Baylor College of Medicine, 77030 Houston, Texas, USA.

Correspondence to: Markus Grompe1 e-mail: grompem@ohsu.edu

* In the HTML version of this article initially published, the statement that the authors had no competing financial interests was incorrect. The authors declare competing financial interests and the details have now been posted online. The error has been corrected in the HTML version of the article.

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