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Comparative Study between the 3D-Liver Spheroid Models Developed from HepG2 and Immortalized Hepatocyte-Like Cells with Primary Hepatic Stellate Coculture for Drug Metabolism Analysis and Anticancer Drug Screening
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Document Title
Comparative Study between the 3D-Liver Spheroid Models Developed from HepG2 and Immortalized Hepatocyte-Like Cells with Primary Hepatic Stellate Coculture for Drug Metabolism Analysis and Anticancer Drug Screening
Author
Sae-be A. Wiwatpanit T. Varatthan T. Namporn T. Laungkulldej S. Thiabma R. Jaiboonma A. Sa-ngiamsuntorn K. Elson D. Porter A.E. Sathirakul K. Hongeng S. Ruenraroengsak P.
Affiliations
Department of Pharmacy Faculty of Pharmacy Mahidol University 447 Sri-Ayutthaya Rd Bangkok Rajathevi 10400 Thailand; National Center for Genetic Engineering and Biotechnology (BIOTEC) National Science and Technology Development Agency (NSTDA) Pathum Thani 10200 Thailand; Department of Pediatrics Faculty of Medicine Ramathibodi Hospital Mahidol University Rama VI Rd Bangkok Rajathevi 10400 Thailand; Department of Biochemistry Faculty of Pharmacy Mahidol University 447 Sri-Ayutthaya Rd Bangkok Rajathevi 10400 Thailand; Department of Surgery and Cancer Imperial College London South Kensington Campus Exhibition Road London SW7 2AZ United Kingdom; Department of Materials and London Centre for Nanotechnology Imperial College London Exhibition Road London SW7 2AZ United Kingdom
Type
Article
Source Title
Advanced Therapeutics
ISSN
23663987
Year
2023
Volume
6
Issue
2
Open Access
All Open Access Hybrid Gold Green
Publisher
John Wiley and Sons Inc
DOI
10.1002/adtp.202200169
Abstract
Liver spheroids may be the best alternative models for evaluating efficacy and toxicity of the new anticancer candidates and diagnostics for hepatocellular carcinoma (HCC). Here novel 3D-liver spheroid models are constructed from human hepatoma cells (HepG2)/ immortalized human hepatocyte-like cells (imHCs) with primary hepatic stellate cells (HSCs) coculture using the ultralow attachment technique. Spheroid morphology HSC distribution metabolic activity protein expressions and drug penetration are evaluated. All developed 3D spheroid models exhibit in spherical shape with narrow size distribution diameter between 639�3 (HepG2-10%HSC) and 519�1 (imHC-10%HSC) ?m. Both imHC mono and coculture models significantly express normal liver biomarkers at the higher level than HepG2 models. While 3D-HepG2 models significantly exhibit HCC biomarkers at the higher level than imHC models. HepG2 and imHC spheroids express basal cytochrom P450 (CYP450) enzymes at different levels depending on cell types culture period and ratio of coculture. Their metabolic activities for dextromethorphan (CYP2D6) tolbutamide (CYP2C9) and midazolam (CYP3A4) are routinely evaluated. For midazolam metabolism imHC models allow the detection of phase II metabolic enzymes (UGT2B4 and UGT2B7). The presence of HSC in HepG2-HSC model increases biological barrier for doxorubicin (DOX) penetration and escalates IC50 of DOX from 61.4 to 127.2�g mL?1. ? 2022 The Authors. Advanced Therapeutics published by Wiley-VCH GmbH.
Industrial Classification
Knowledge Taxonomy Level 1
Knowledge Taxonomy Level 2
Knowledge Taxonomy Level 3
License
CC BY-NC-ND
Rights
Authors
Publication Source
WOS