ArticlePloS one2015
A novel mouse model for stable engraftment of a human immune system and human hepatocytes.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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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
50 citing papers in PubMed.
- Advancement of humanized mice and leading applications in immunological disease models.Inflammation and regeneration · 2026Review
- Functional immune responses induced by a capsid assembly modulator in chronic hepatitis B virus-infected humanized mice.Cell host & microbe · 2026Article
- Current Treatment Regimens and Promising Molecular Therapies for Chronic Hepatobiliary Diseases.Biomolecules · 2025Review
- Mice Engrafted with Human Liver Cells.Seminars in liver disease · 2024Review
- Review
- Conversion of hepatitis B virus relaxed circular to covalently closed circular DNA is supported in murine cells.JHEP reports : innovation in hepatology · 2022Article
- Liver-humanized mice: A translational strategy to study metabolic disorders.Journal of cellular physiology · 2022Review
- Can next-generation humanized mice that reconstituted with both functional human immune system and hepatocytes model the progression of viral hepatitis to hepatocarcinogenesis?Frontiers in medicine · 2022Review
- In vitro functional analysis of gRNA sites regulating assembly of hepatitis B virus.Communications biology · 2021Article
- Are Humanized Mouse Models Useful for Basic Research of Hepatocarcinogenesis through Chronic Hepatitis B Virus Infection?Viruses · 2021Review
- Advancing our understanding of HIV co-infections and neurological disease using the humanized mouse.Retrovirology · 2021Review
- Animal Models of Hepatitis B Virus Infection-Success, Challenges, and Future Directions.Viruses · 2021Review
- Review
- Establishment of Humanized Mice for the Study of HBV.Frontiers in immunology · 2021Review
- Potent human broadly neutralizing antibodies to hepatitis B virus from natural controllers.The Journal of experimental medicine · 2020Article
- Experimental Variables that Affect Human Hepatocyte AAV Transduction in Liver Chimeric Mice.Molecular therapy. Methods & clinical development · 2020Article
- Innovations, challenges, and minimal information for standardization of humanized mice.EMBO molecular medicine · 2020Review
- Immune Response Mechanisms against AAV Vectors in Animal Models.Molecular therapy. Methods & clinical development · 2020Review
- Animal Models Used in Hepatitis C Virus Research.International journal of molecular sciences · 2020Review
- Art of Making Artificial Liver: Depicting Human Liver Biology and Diseases in Mice.Seminars in liver disease · 2020Review
Corrections and comments
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Authors and funding
12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatic infections by hepatitis B virus (HBV), hepatitis C virus (HCV) and Plasmodium parasites leading to acute or chronic diseases constitute a global health challenge. The species tropism of these hepatotropic pathogens is restricted to chimpanzees and humans, thus model systems to study their pathological mechanisms are severely limited. Although these pathogens infect hepatocytes, disease pathology is intimately related to the degree and quality of the immune response. As a first step to decipher the immune response to infected hepatocytes, we developed an animal model harboring both a human immune system (HIS) and human hepatocytes (HUHEP) in BALB/c Rag2-/- IL-2Rγc-/- NOD.sirpa uPAtg/tg mice. The extent and kinetics of human hepatocyte engraftment were similar between HUHEP and HIS-HUHEP mice. Transplanted human hepatocytes were polarized and mature in vivo, resulting in 20-50% liver chimerism in these models. Human myeloid and lymphoid cell lineages developed at similar frequencies in HIS and HIS-HUHEP mice, and splenic and hepatic compartments were humanized with mature B cells, NK cells and naïve T cells, as well as monocytes and dendritic cells. Taken together, these results demonstrate that HIS-HUHEP mice can be stably (> 5 months) and robustly engrafted with a humanized immune system and chimeric human liver. This novel HIS-HUHEP model provides a platform to investigate human immune responses against hepatotropic pathogens and to test novel drug strategies or vaccine candidates.
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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.