ArticleProceedings of the National Academy of Sciences of the United States of America2020
Expansion, in vivo-ex vivo cycling, and genetic manipulation of primary human hepatocytes.
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Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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49citing papers in PubMed
5.3field-weighted citation impact, top 3% of its field
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Who cites it
49 citing papers in PubMed, 59 citations in OpenAlex.
- Transient culture of adult human hepatocytes as organoids improves engineered liver engraftment.Biomaterials · 2027Article
- Hepatitis B virus protein X promotes survival and loss of hepatocyte identity in a differentiated human liver organoid system.Cell death and differentiation · 2026Article
- The HBV basal core promoter mutation confers a replicative advantage and transcriptionally reprograms hepatocytes toward HCC subtypes.bioRxiv : the preprint server for biology · 2026Article
- 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
- Orthogonal CRISPR screens and human liver chimeric mice identify hepatitis B virus host factors.bioRxiv : the preprint server for biology · 2026Article
- Hepatocyte Models for Metabolic Dysfunction-Associated Steatotic Liver Disease: A Comparative Analysis of Non-HepG2 Cell Models.International journal of molecular sciences · 2026Review
- Hepatitis B virus covalently closed circular DNA formation in murine hepatic cells uncovers a late entry block.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Factor VIII originates primarily from anatomically distinct subsets of liver sinusoidal endothelial cells.Blood advances · 2026Article
- [Advances in the construction and application of a novel liver organoid model for hepatitis B virus infection].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2026Review
- Experimental models of liver-stage malaria: Progress, gaps, and challenges.PLoS pathogens · 2025Review
- Achieving scalable expansion of therapeutic porcine hepatocytes in vivo through serial transplantation.Animal models and experimental medicine · 2025Article
- Experimental Models to Investigate PNPLA3 in Liver Steatosis.Liver international : official journal of the International Association for the Study of the Liver · 2025Review
- Halting Hypercaloric Feeding in Liver Chimeric Mice Rapidly Resolves Human Hepatocyte Steatosis.Gastro hep advances · 2025Article
- Hydrogel-Based Strategies for Liver Tissue Engineering.Chem & bio engineering · 2024Review
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- Mice Engrafted with Human Liver Cells.Seminars in liver disease · 2024Review
- Increased Protein Kinase A Activity Induces Fibrolamellar Hepatocellular Carcinoma Features Independent of DNAJB1.Cancer research · 2024Article
- Technical evaluation and standardization of the human thyroid microtissue assay.Toxicological sciences : an official journal of the Society of Toxicology · 2024Article
- Hepatitis B: Model Systems and Therapeutic Approaches.Journal of immunology research · 2024Review
Corrections and comments
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Authors and funding
26 authors at 12 institutions in 7 countries.
Eleftherios MichailidisLaboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065.
Koen VercauterenLaboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065.
Liliana Mancio-SilvaInstitute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02142.ORCID 0000-0002-5585-018X
Linda AndrusLaboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065.
Cyprien JahanLaboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065.
Inna Ricardo-LaxLaboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065.ORCID 0000-0002-9590-9692
Chenhui ZouLaboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065.
Mohammad KabbaniLaboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065.
Paul ParkLaboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065.
Corrine QuirkLaboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065.
Christina PyrgakiBio-Imaging Resource Center, The Rockefeller University, New York, NY 10065.
Brandon RazookyLaboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065.
Lieven VerhoyeLaboratory of Liver Infectious Diseases, Ghent University, 9000 Ghent, Belgium.
Irene ZoluthkinDivision of Cellular and Molecular Therapy, Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL 32607.
Wei-Yu LuMedical Research Council Centre for Regenerative Medicine, University of Edinburgh, Edinburgh EH16 4TJ, United Kingdom.
Stuart J ForbesMedical Research Council Centre for Regenerative Medicine, University of Edinburgh, Edinburgh EH16 4TJ, United Kingdom.
Luis ChiribogaDepartment of Pathology, NYU Langone Health, New York, NY 10003.
Neil D TheiseDepartment of Pathology, NYU Langone Health, New York, NY 10003.
Roland W HerzogDivision of Cellular and Molecular Therapy, Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL 32607.
Hiroshi SuemizuLaboratory Animal Research Department, Central Institute for Experimental Animals, Kawasaki 210-0821, Japan.
William M SchneiderLaboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065.
Amir ShlomaiDepartment of Medicine D and the Liver Institute, Rabin Medical Center, Belinson Hospital, Petach-Tikva 49100, Israel.ORCID 0000-0001-7437-9381
Philip MeulemanLaboratory of Liver Infectious Diseases, Ghent University, 9000 Ghent, Belgium.
Sangeeta N BhatiaInstitute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02142.
Charles M RiceLaboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065; ricec@rockefeller.edu ydj2001@med.cornell.edu.
Ype P de JongLaboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065; ricec@rockefeller.edu ydj2001@med.cornell.edu.
Rockefeller University · USGhent University Hospital · BECornell University · USMRC Centre for Regenerative Medicine · GBNYU Langone Health · USUniversity of Florida · USBroad Institute · USCentral Institute for Experimental Animals · JPÉcole Normale Supérieure Paris-Saclay · FRHeidelberg University · DEMassachusetts Institute of Technology · USTel Aviv University · IL
Funding
VIRUS PRODUCTION COREP30CA014051 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI Paula T Hammond · 1985 to 2026
$93.9MEnhancing immune regulation in gene therapy for hemophiliaR01HL131093 · NHLBI · UNIVERSITY OF FLORIDA · PI Ype Peter De Jong, Roland W. Herzog · 2016 to 2026
$7.2MModeling human hepatotropic infections in complex tissue organoidsR01DK085713 · NIDDK · ROCKEFELLER UNIVERSITY · PI BHATIA, SANGEETA N., RICE, CHARLES M · 2009 to 2013
$5.6MType I interferon-stimulated genes and the antiviral immune responseR01AI091707 · NIAID · ROCKEFELLER UNIVERSITY · PI RICE, CHARLES M · 2011 to 2020
$5.5MIn search of an HBV cure: novel model systems and targetsR01AI143295 · NIAID · ROCKEFELLER UNIVERSITY · PI RICE, CHARLES M · 2019 to 2023
$3.0MModeling alcohol toxicity in human hepatocytesR01AA027327 · NIAAA · WEILL MEDICAL COLL OF CORNELL UNIV · PI DE JONG, YPE PETER · 2019 to 2023
$1.9MThe role of innate immune evasion in hepatitis C virus infectionK08DK090576 · NIDDK · WEILL MEDICAL COLL OF CORNELL UNIV · PI DE JONG, YPE PETER · 2011 to 2015
$760kThe role of innate immune response in HBV infection and persistenceF32DK107164 · NIDDK · ROCKEFELLER UNIVERSITY · PI MICHAILIDIS, ELEFTHERIOS · 2015 to 2017
$179kHoward Hughes Medical InstituteMedical Research Council MR/K017047/1NCI NIH HHS P30 CA014051NHLBI NIH HHS R01 HL131093NIAAA NIH HHS R01 AA027327NIAID NIH HHS R01 AI091707NIAID NIH HHS R01 AI143295NIDDK NIH HHS F32 DK107164NIDDK NIH HHS K08 DK090576NIDDK NIH HHS R01 DK085713
Abstract
Primary human hepatocytes (PHHs) are an essential tool for modeling drug metabolism and liver disease. However, variable plating efficiencies, short lifespan in culture, and resistance to genetic manipulation have limited their use. Here, we show that the pyrrolizidine alkaloid retrorsine improves PHH repopulation of chimeric mice on average 10-fold and rescues the ability of even poorly plateable donor hepatocytes to provide cells for subsequent ex vivo cultures. These mouse-passaged (mp) PHH cultures overcome the marked donor-to-donor variability of cryopreserved PHH and remain functional for months as demonstrated by metabolic assays and infection with hepatitis B virus and
Indexed as
AnimalsCell TransplantationChimeraDisease Models, AnimalFemaleGenetic TherapyHepatitis BHepatitis B virusHepatocytesHomeodomain ProteinsHumansHydrolasesInterleukin Receptor Common gamma SubunitLiverLiver DiseasesMalariafumarylacetoacetaseHomeodomain ProteinsHydrolasesIl2rg protein, mouseInterleukin Receptor Common gamma SubunitPyrrolizidine AlkaloidsRAG-1 proteinretrorsinehepatitis B virushepatotropic pathogenshumanized miceliverprimary human hepatocytes
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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.