ArticleThe American journal of pathology2004
Near completely humanized liver in mice shows human-type metabolic responses to drugs.
Article in The American journal of pathology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 174 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
174 citing papers in PubMed, 541 citations in OpenAlex.
- An oral, liver-restricted LXR inverse agonist for dyslipidemia: preclinical development and phase 1 trial.Nature medicine · 2026Trial
- Antiviral effects of anti-HBs immunoglobulin and vaccine on HBs antigen seroclearance for chronic hepatitis B infection.Journal of gastroenterology · 2016Trial
- The making of cells and organs in xenogeneic animal bioreactor.Signal transduction and targeted therapy · 2026Review
- Cell-based platforms for antiviral screening against hepatitis B virus: advantages, limitations, and future perspectives.Antiviral research · 2026Review
- Application of chimeric mice with human hepatocytes for the evaluation of metabolically activated genotoxic substances.Genes and environment : the official journal of the Japanese Environmental Mutagen Society · 2026Article
- Stable state of hepatocyte chromatin during hepatitis B virus infection.Scientific reports · 2026Article
- Recent advances in the construction of humanized animal models and applications in translational medicine.Animal models and experimental medicine · 2026Review
- Development of a Novel Human Hepatoma Cell Line Supporting the Replication of a Recombinant HBV Genome with a Reporter Gene.Viruses · 2026Article
- An evaluation of the human relevance of the hepatocellular tumors observed in mice treated with synthetic fungicide, pyridachlometyl, based on mode of action.Archives of toxicology · 2025Article
- Development of human growth hormone-treated chimeric mice with humanized livers for an evaluation model of drug-induced fatty liver disease.Archives of toxicology · 2025Article
- Cell therapy for liver disorders: past, present and future.Nature reviews. Gastroenterology & hepatology · 2025Review
- Investigation of Biotransformation Pathways in a Chimeric Mouse with a Humanized Liver.International journal of molecular sciences · 2025Article
- Generation of Replication-Competent Hepatitis B Virus Harboring Tagged Polymerase for Visualization and Quantification of the Infection.Microbiology and immunology · 2025Article
- Hepatitis B virus genotypes A1 and A2 have distinct replication phenotypes due to polymorphisms in the HBx gene.PLoS pathogens · 2025Article
- Alteration of Gene Expression After Entecavir and Pegylated Interferon Therapy in HBV-Infected Chimeric Mouse Liver.Viruses · 2024Article
- Mice Engrafted with Human Liver Cells.Seminars in liver disease · 2024Review
- Plasma and urinary CP I and CP III concentrations in chimeric mice with human hepatocytes after rifampicin administration.Pharmacology research & perspectives · 2024Article
- Selective depletion of HBV-infected hepatocytes by class A capsid assembly modulators requires high levels of intrahepatic HBV core protein.Antimicrobial agents and chemotherapy · 2024Article
- Transient growth factor expression via mRNA in lipid nanoparticles promotes hepatocyte cell therapy in mice.Nature communications · 2024Article
- Human Hepatocyte Transplantation: Three Decades of Clinical Experience and Future Perspective.Stem cells translational medicine · 2024Review
114 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human hepatocytes were transplanted into urokinase-type plasminogen activator-transgenic SCID mice (uPA/SCID mice), which are immunodeficient and undergo liver failure. The transplanted cells were characterized in terms of their in vivo growth potential and functions. The human hepatocytes progressively repopulated the murine host liver. However, the recipients died when the replacement index (RI) of the human hepatocytes exceeded 50%. The hosts (chimeric mice) survived at RI >50% when treated with a drug that has anti-human complement factor activity, and these mice developed livers with RI values as high as 96%. In total, 36 chimeric mice were generated, and the rate of successful engraftment was as high as 92%. The yield of chimeric mice with RI >70% was 32%. The human hepatocytes in the murine host liver expressed mRNAs for a variety of human cytochrome P450 (hCYP) subtypes, in a manner that was similar to the donor liver. The mRNAs for hCYP3A4 and hCYP1A1/2 were induced in the liver in a CYP type-specific manner when the mice were treated with rifampicin and 3-methylcholanthrene, respectively. These results indicate that human hepatocytes that propagate in mice retain their normal pharmacological responses. We conclude that the chimeric mouse developed in the present study is a useful model for assessing the functions and pharmacological responses of human hepatocytes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.