The liver is the metabolic core of the whole body. Tools commonly used to study the human liver metabolism include hepatocyte cell lines, primary human hepatocytes, and pluripotent stem cells-derived hepatocytes in vitro, and liver genetically humanized mouse model in vivo. However, none of these systems can mimic the human liver in physiological and pathological states satisfactorily. Liver-humanized mice, which are established by reconstituting mouse liver with human hepatocytes, have emerged as an attractive animal model to study drug metabolism and evaluate the therapeutic effect in "human liver" in vivo because the humanized livers greatly replicate enzymatic features of human hepatocytes. The application of liver-humanized mice in studying metabolic disorders is relatively less common due to the largely uncertain replication of metabolic profiles compared to humans. Here, we summarize the metabolic characteristics and current application of liver-humanized mouse models in metabolic disorders that have been reported in the literature, trying to evaluate the pros and cons of using liver-humanized mice as novel mouse models to study metabolic disorders.
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http://dx.doi.org/10.1002/jcp.30610 | DOI Listing |
Sci Rep
December 2024
The Program for Experimental and Theoretical Modeling, Division of Hepatology, Department of Medicine, Stritch School of Medicine, Loyola University Chicago, 2160 S. First Ave., Maywood, IL, 60153, USA.
Designing and carrying out a controlled human infection (CHI) model for hepatitis C virus (HCV) is critical for vaccine development. However, key considerations for a CHI model protocol include understanding of the earliest viral-host kinetic events during the acute phase and susceptibility of the viral isolate under consideration for use in the CHI model to antiviral treatment before any infections in human volunteers can take place. Humanized mouse models lack adaptive immune responses but provide a unique opportunity to obtain quantitative understanding of early HCV kinetics and develop mathematical models to further understand viral and innate immune response dynamics during acute HCV infection.
View Article and Find Full Text PDFEMBO Mol Med
April 2024
Center for Global Infectious Disease Research, Seattle Children's Research Institute, 307 Westlake Avenue North, Suite 500, Seattle, WA, 98109, USA.
Vaccination with infectious Plasmodium falciparum (Pf) sporozoites (SPZ) administered with antimalarial drugs (PfSPZ-CVac), confers superior sterilizing protection against infection when compared to vaccination with replication-deficient, radiation-attenuated PfSPZ. However, the requirement for drug administration constitutes a major limitation for PfSPZ-CVac. To obviate this limitation, we generated late liver stage-arresting replication competent (LARC) parasites by deletion of the Mei2 and LINUP genes (mei2/linup or LARC2).
View Article and Find Full Text PDFHepatol Commun
December 2023
Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan.
Background: HBV DNA integration into the host genome is frequently found in HBV-associated HCC tissues and is associated with hepatocarcinogenesis. Multiple detection methods, including hybrid capture-sequencing, have identified integration sites and provided clinical implications; however, each has advantages and disadvantages concerning sensitivity, cost, and throughput. Therefore, methods that can comprehensively and cost-effectively detect integration sites with high sensitivity are required.
View Article and Find Full Text PDFDrug Metab Dispos
October 2023
Quantitative, Translational & ADME Sciences, AbbVie Deutschland GmbH & Co. KG, Ludwigshafen, Germany (M.M.); Drug Metabolism and Pharmacokinetics, Genentech, Inc., South San Francisco, California (R.S.J., D.S., J.C.C.); Yecuris Corporation, Tualatin, Oregon (D.C.G., L.F.); Clinical Pharmacology, Pharmacometrics, Disposition & Bioanalysis, Bristol Myers Squibb, Lawrenceville, New Jersey (M.H.); Symeres Finland Oy, Oulu, Finland, operating under Admescope brand (A.T.H., J.M.); Global Drug Metabolism and Pharmacokinetics, Takeda Development Center Americas, Inc. Cambridge, Massachusetts (S.P., P.P.C.); and FH Aachen University of Applied Sciences, Jülich, Germany (N.S.).
Numerous biomedical applications have been described for liver-humanized mouse models, such as in drug metabolism or drug-drug interaction (DDI) studies. However, the strong enlargement of the bile acid (BA) pool due to lack of recognition of murine intestine-derived fibroblast growth factor-15 by human hepatocytes and a resulting upregulation in the rate-controlling enzyme for BA synthesis, cytochrome P450 (CYP) 7A1, may pose a challenge in interpreting the results obtained from such mice. To address this challenge, the human fibroblast growth factor-19 (FGF19) gene was inserted into the , , NOD (FRGN) mouse model, allowing repopulation with human hepatocytes capable of responding to FGF19.
View Article and Find Full Text PDFVirology
September 2023
National Institute of Biological Sciences, Beijing, China; Tsinghua Institute of Multidisciplinary Biomedical Research, Tsinghua University, Beijing, 102206, China. Electronic address:
Current therapies control but rarely achieve a cure for hepatitis B virus (HBV) infection. Restoration of the HBV-specific immunity by cell-based therapy represents a potential approach for a cure. In this study, we generated HBV specific CAR T cells based on an antibody 2H5-A14 targeting a preS1 region of the HBV large envelope protein.
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