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Cited by 55Pharmacogenetics and Drug MetabolismAnimal testing and alternativesDrug Transport and Resistance Mechanisms

Can ‘humanized’ mice improve drug development in the 21st century?

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Peltz, Gary·2013·Trends in Pharmacological Sciences
DOI 10.1016/j.tips.2013.03.005PMC PMC3682766
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Abstract

Chimeric mice, which have human hepatocytes engrafted in their liver, have been used to study human drug metabolism and pharmacodynamic responses for nearly 20 years. However, there are very few examples where their use has prospectively impacted the development of a candidate medication. Here, three different chimeric mouse models and their utility for pharmacology studies are evaluated. Several recent studies indicate that using these chimeric mouse models could help to overcome traditional (predicting human-specific metabolites and toxicities) and 21st century problems (strategies for personalized medicine and selection of optimal combination therapies) in drug development. These examples suggest that there are many opportunities in which the use of chimeric mice could significantly improve the quality of preclinical drug assessment.

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  • Recent advances in modelling liver diseases include generation of mice with a chimeric liver, where hepatocytes are replaced with those of human origin, to better mimic the physiology and microenvironment of the human liver.

    “Recent advances in modelling of liver diseases include generation of mice with a chimeric liver; that is where the hepatocytes are replaced with those of human origin, to better mimic the physiology and microenvironment of the human liver(54).”

    From The liver as a central "hub" of the immune system: pathophysiological implications (2025) · cites this paper as [54]

    The 'Modeling Human Drug Metabolism and Drug Response' section describes mice whose livers are repopulated with transplanted human liver cells. The 'Different engineering leads to different performance' section reports human-like liver functions and, for one model, a mature three-dimensional architecture. The paper focuses on drug metabolism and does not establish that these mice reproduce the human liver microenvironment for modelling liver diseases. Page numbers are unavailable in our copy. (LLM, conf=0.85)

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  • The ASH liver exhibits an increase in infiltrating monocytes, diversifying the intrahepatic macrophage pool so that it consists of embryonic-derived bona fide KCs and monocyte-derived macrophages.

    “The ASH liver also exhibits an increase in infiltrating monocytes, diversifying the intrahepatic macrophage pool so that it consists of embryonic-derived bona fide KCs and monocytederived macrophages (54).”

    From The liver as a central "hub" of the immune system: pathophysiological implications (2025) · cites this paper as [54]

    The ‘Different engineering leads to different performance’ and ‘Moving forward’ sections discuss humanized mouse livers and drug toxicity, not macrophage populations in ASH. Searches for infiltrating monocytes, Kupffer cells, and macrophage origins found no passage addressing the claim; page numbers were not available in our copy. (LLM, conf=0.76)

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Research works printed but not linked: 35

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Authors
Peltz, G.
Affiliations
Stanford Medicine (US)
Corresponding author
Peltz, Gary
ORCID
Peltz, Gary
Venue
Trends in Pharmacological Sciences
Publisher
Elsevier BV
Published
2013-05
Volume
34
Issue
5
Pages
255-260
ISSN
0165-6147 (ISSN-L)
DOI
10.1016/j.tips.2013.03.005
PMC
PMC3682766
OpenAlex
W2011452727
Cited by
55
References
2
Citations by year
2026: 3 · 2024: 2 · 2023: 9 · 2022: 4 · 2021: 3 · 2020: 2 · 2019: 2 · 2018: 2 · 2017: 2 · 2016: 6 · 2015: 7 · 2014: 7 · 2013: 6
FWCI
1.42
Type
journal article
Language
en
Open access
Locations
  • Trends in Pharmacological Sciences (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute of Diabetes and Digestive and Kidney Diseases (R01DK090992)
Topics
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
  • Health Sciences › Veterinary › Small Animals › Animal testing and alternatives
  • Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
Keywords
chimeric mice, humanized mice, drug metabolism, pharmacodynamics, personalized medicine, combination therapy, drug toxicity prediction, drug development
MeSH terms
Animals, Chimera, Humans, Liver, Mice, Knockout, Toxicity Tests, Models, Animal, Mice, Drug Discovery

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