Cited by 835Xenotransplantation and immune responseLiver physiology and pathologyTissue Engineering and Regenerative Medicine

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

Open access
Azuma, Hisaya, Paulk, Nicole, Ranade, Aarati, Dorrell, Craig, Al-Dhalimy, Muhsen, Ellis, Ewa, Strom, Stephen, Kay, Mark A +2 more·2007·Nature Biotechnology

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.

Integrity signals

Registry

Crossref · 10.1038/nbt1326

Cites

42 of 42 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Azuma, H., Paulk, N., Ranade, A., Dorrell, C., Al-Dhalimy, M., Ellis, E., Strom, S., Kay, M. A., Finegold, M., & Grompe, M.
Affiliations
  • Oregon Health & Science University (US)
  • University of Pittsburgh Medical Center (US)
  • Stanford University (US)
  • Baylor College of Medicine (US)
Corresponding author
Grompe, Markus
Venue
Nature Biotechnology
Published
2007-07-29
Volume
25
Issue
8
Pages
903-910
ISSN
  • 0733-222X (ISSN-L)
  • 1087-0156
  • 1546-1696
OpenAlex
W2162807448
Cited by
835
References
42
Citations by year
2026: 33 · 2025: 28 · 2024: 43 · 2023: 37 · 2022: 55 · 2021: 55 · 2020: 60 · 2019: 47 · 2018: 59 · 2017: 60 · 2016: 41 · 2015: 56 · 2014: 58 · 2013: 52 · 2012: 44
FWCI
26.55
Type
journal article
Language
en
Open access
Locations
  • Nature Biotechnology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (n01dk092310-000)
  • National Cancer Institute (F31CA130116)
  • National Institute of General Medical Sciences (GM06346)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01DK048252, R01-DK48252, DK-92310)
  • U.S. National Library of Medicine (N01 DK092310)
Topics
  • Health Sciences › Medicine › Surgery › Xenotransplantation and immune response
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
  • Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
Keywords
human hepatocytes, liver xenotransplantation, fumarylacetoacetate hydrolase, immunodeficient mice, serial transplantation, drug metabolism
MeSH terms
Animals, DNA-Binding Proteins, Humans, Hydrolases, Mice, Knockout, Cell Culture Techniques, Hepatocytes, Tissue Engineering, Mice, Interleukin Receptor Common gamma Subunit

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review