ArticlePloS one2020
Culture density contributes to hepatic functions of fresh human hepatocytes isolated from chimeric mice with humanized livers: Novel, long-term, functional two-dimensional in vitro tool for developing new drugs.
Article in PloS one, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 40 citations in OpenAlex.
- Methodological innovations in perfusable vascular networks: Advancing high-density tissue models.Regenerative therapy · 2026Article
- Metabolism-dependent drug response assessment using a liver-cancer microphysiological system on the kinetic-pump integrated microfluidic plate (KIM-Plate).NAM journal · 2026Article
- Microengineered discoid liver platforms: bridging geometry, functions, and scalability.Annals of translational medicine · 2025Article
- Netrin-1 inhibits the attachment and internalization of Hepatitis B virus for hepatocyte infection.PLoS pathogens · 2025Article
- Modeling of hepatitis B virus infection spread in primary human hepatocytes.Journal of virology · 2025Article
- Temporal changes of hepatic drug-metabolizing enzymes mediated by hepatic ischemia-reperfusion injury and the protective effect of Oridonin.Scientific reports · 2025Article
- Species-specific gene expression manipulation in humanized livers of chimeric mice via siRNA-encapsulated lipid nanoparticle treatment.Molecular therapy. Methods & clinical development · 2025Article
- In vitro liver models for toxicological research.Drug metabolism and pharmacokinetics · 2025Review
- Modeling of hepatitis B virus kinetics and accumulation of cccDNA in primary human hepatocytes.JHEP reports : innovation in hepatology · 2025Article
- Liver-derived Neuregulin1α stimulates compensatory pancreatic β cell hyperplasia in insulin resistance.Nature communications · 2025Article
- Plasma and urinary CP I and CP III concentrations in chimeric mice with human hepatocytes after rifampicin administration.Pharmacology research & perspectives · 2024Article
- Gut-liver microphysiological systems revealed potential crosstalk mechanism modulating drug metabolism.PNAS nexus · 2024Article
- Cryopreservation of assay-ready hepatocyte monolayers by chemically-induced ice nucleation: preservation of hepatic function and hepatotoxicity screening capabilities.Biomaterials science · 2023Article
- Culture methods focusing on bile canalicular formation using primary human hepatocytes in a short time.In vitro cellular & developmental biology. Animal · 2023Article
- Induction of open-form bile canaliculus formation by hepatocytes for evaluation of biliary drug excretion.Communications biology · 2023Article
- Persistent hepatic IFN system activation in HBV-HDV infection determines viral replication dynamics and therapeutic response.JCI insight · 2023Article
- Long-term cell fate and functional maintenance of human hepatocyte through stepwise culture configuration.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023Article
- Consideration of Commercially Available Hepatocytes as Cell Sources for Liver-Microphysiological Systems by Comparing Liver Characteristics.Pharmaceutics · 2022Article
- Assay-ready Cryopreserved Cell Monolayers Enabled by Macromolecular Cryoprotectants.Biomacromolecules · 2022Article
- Contribution of Humanized Liver Chimeric Mice to the Study of Human Hepatic Drug Transporters: State of the Art and Perspectives.European journal of drug metabolism and pharmacokinetics · 2022Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chimeric mice with humanized livers are considered a useful animal model for predicting human (h-) drug metabolism and toxicity. In this study, the characteristics of fresh h-hepatocytes (cFHHs, PXB-cells®) isolated from chimeric mice (PXB-mice®) were evaluated in vitro to confirm their utility for drug development. cFHHs cultured at high density (2.13 × 105 cells/cm2) displayed stable production of h-albumin and cytochrome P450 (CYP) 3A activities for at least 21 days. The mRNA expression levels of 10 of 13 CYP, UDP-glucuronosyltransferase (UGT), and transporters were maintained at >10% of the levels of freshly isolated cFHHs after 21 days. From 1 week, many bile canaliculi were observed between cFHHs, and the accumulation of the multidrug resistance-associated protein and bile salt export pump substrates in these bile canaliculi was clearly inhibited by cyclosporin A. Microarray analysis of cFHHs cultured at high density and at low density (0.53 × 105 cells/cm2) revealed that high density culture maintained high expressions of some transcription factors (HNF4α, PXR, and FXR) perhaps involved in the high CYP, UGT and transporter gene expressions of cFHHs. These results strongly suggest that cFHHs could be a novel in vitro tool for drug development studies.
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