Functional Liver Cell–Based Platforms in Biomedical Research

ABSTRACT Recapitulating in vivo conditions of metabolism remains a challenging subject in biomedical research such as ADME‐Tox assays (absorption, distribution, metabolism, excretion, and toxicity). The advanced technologies using 3D co‐culture methods enabled researchers to develop cell–cell and ce...

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Published inPHARMACOLOGY RESEARCH & PERSPECTIVES Vol. 13; no. 3; pp. e70128 - n/a
Main Authors Hashemian, Zohreh, Taleahmad, Sara, Shokouhian, Bahare, Najimi, Mustapha, Vosough, Massoud
Format Journal Article Publication
LanguageEnglish
Published United States John Wiley & Sons, Inc 01.06.2025
John Wiley and Sons Inc
Wiley
Subjects
Animals
biomedical research
Biomedical Research - methods
Carcinoma, Hepatocellular - metabolism
Carcinoma, Hepatocellular - pathology
Coculture Techniques - methods
Drug development
Drug Evaluation, Preclinical - methods
drug screening platforms
hepatocytes
Hepatocytes - cytology
Hepatocytes - metabolism
hepatoma cells
Humans
improved metabolic performance
Liver - cytology
Liver - metabolism
Liver Neoplasms - metabolism
Liver Neoplasms - pathology
Metabolites
Review
Stem cells
Toxicity
drug screening platforms
improved metabolic performance
hepatocytes
hepatoma cells
biomedical research
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Abstract ABSTRACT Recapitulating in vivo conditions of metabolism remains a challenging subject in biomedical research such as ADME‐Tox assays (absorption, distribution, metabolism, excretion, and toxicity). The advanced technologies using 3D co‐culture methods enabled researchers to develop cell–cell and cell–extracellular matrix (ECM) interactions similar to the natural liver, resulting in the improvement of the metabolic performance of ex vivo cultured primary hepatocytes (PHs). Although PHs are the best candidates in cell‐based drug screening methods, access to these cells is limited. The application of stem cell–derived hepatocyte‐like cells (HLCs) could overcome these limitations in high‐throughput assessments. However, the functional capacity of HLCs is not enough. Hepatoma cells could be reliable substitutes for PHs and HLCs; however, compared to PHs, their metabolic performance is low. Mimicking the complexity of the liver microenvironment using hepatoma cells and liver‐specific stromal cells in a 3D culture condition represents an innovative, accessible, and scalable platform to accelerate drug development if the metabolic capacity of hepatoma cells is enhanced. This can reduce time, costs, and address the ethical concerns related to animal models and pluripotent stem cells. In this manuscript, we showed that mimicking the complexity of the liver microenvironment in a 3D co‐culture condition with non‐parenchymal cells and improving the metabolic performance of hepatoma cells represents an innovative and accessible platform to accelerate drug discovery and development. Exploring various sources for hepatocytes: Advantages and disadvantages of each source of cells; foundations for advancements in the ADME‐Tox assay.
AbstractList ABSTRACT Recapitulating in vivo conditions of metabolism remains a challenging subject in biomedical research such as ADME‐Tox assays (absorption, distribution, metabolism, excretion, and toxicity). The advanced technologies using 3D co‐culture methods enabled researchers to develop cell–cell and cell–extracellular matrix (ECM) interactions similar to the natural liver, resulting in the improvement of the metabolic performance of ex vivo cultured primary hepatocytes (PHs). Although PHs are the best candidates in cell‐based drug screening methods, access to these cells is limited. The application of stem cell–derived hepatocyte‐like cells (HLCs) could overcome these limitations in high‐throughput assessments. However, the functional capacity of HLCs is not enough. Hepatoma cells could be reliable substitutes for PHs and HLCs; however, compared to PHs, their metabolic performance is low. Mimicking the complexity of the liver microenvironment using hepatoma cells and liver‐specific stromal cells in a 3D culture condition represents an innovative, accessible, and scalable platform to accelerate drug development if the metabolic capacity of hepatoma cells is enhanced. This can reduce time, costs, and address the ethical concerns related to animal models and pluripotent stem cells. In this manuscript, we showed that mimicking the complexity of the liver microenvironment in a 3D co‐culture condition with non‐parenchymal cells and improving the metabolic performance of hepatoma cells represents an innovative and accessible platform to accelerate drug discovery and development.
Recapitulating in vivo conditions of metabolism remains a challenging subject in biomedical research such as ADME-Tox assays (absorption, distribution, metabolism, excretion, and toxicity). The advanced technologies using 3D co-culture methods enabled researchers to develop cell-cell and cell-extracellular matrix (ECM) interactions similar to the natural liver, resulting in the improvement of the metabolic performance of ex vivo cultured primary hepatocytes (PHs). Although PHs are the best candidates in cell-based drug screening methods, access to these cells is limited. The application of stem cell-derived hepatocyte-like cells (HLCs) could overcome these limitations in high-throughput assessments. However, the functional capacity of HLCs is not enough. Hepatoma cells could be reliable substitutes for PHs and HLCs; however, compared to PHs, their metabolic performance is low. Mimicking the complexity of the liver microenvironment using hepatoma cells and liver-specific stromal cells in a 3D culture condition represents an innovative, accessible, and scalable platform to accelerate drug development if the metabolic capacity of hepatoma cells is enhanced. This can reduce time, costs, and address the ethical concerns related to animal models and pluripotent stem cells. In this manuscript, we showed that mimicking the complexity of the liver microenvironment in a 3D co-culture condition with non-parenchymal cells and improving the metabolic performance of hepatoma cells represents an innovative and accessible platform to accelerate drug discovery and development.
Recapitulating in vivo conditions of metabolism remains a challenging subject in biomedical research such as ADME‐Tox assays (absorption, distribution, metabolism, excretion, and toxicity). The advanced technologies using 3D co‐culture methods enabled researchers to develop cell–cell and cell–extracellular matrix (ECM) interactions similar to the natural liver, resulting in the improvement of the metabolic performance of ex vivo cultured primary hepatocytes (PHs). Although PHs are the best candidates in cell‐based drug screening methods, access to these cells is limited. The application of stem cell–derived hepatocyte‐like cells (HLCs) could overcome these limitations in high‐throughput assessments. However, the functional capacity of HLCs is not enough. Hepatoma cells could be reliable substitutes for PHs and HLCs; however, compared to PHs, their metabolic performance is low. Mimicking the complexity of the liver microenvironment using hepatoma cells and liver‐specific stromal cells in a 3D culture condition represents an innovative, accessible, and scalable platform to accelerate drug development if the metabolic capacity of hepatoma cells is enhanced. This can reduce time, costs, and address the ethical concerns related to animal models and pluripotent stem cells. In this manuscript, we showed that mimicking the complexity of the liver microenvironment in a 3D co‐culture condition with non‐parenchymal cells and improving the metabolic performance of hepatoma cells represents an innovative and accessible platform to accelerate drug discovery and development. Exploring various sources for hepatocytes: Advantages and disadvantages of each source of cells; foundations for advancements in the ADME‐Tox assay.
ABSTRACT Recapitulating in vivo conditions of metabolism remains a challenging subject in biomedical research such as ADME‐Tox assays (absorption, distribution, metabolism, excretion, and toxicity). The advanced technologies using 3D co‐culture methods enabled researchers to develop cell–cell and cell–extracellular matrix (ECM) interactions similar to the natural liver, resulting in the improvement of the metabolic performance of ex vivo cultured primary hepatocytes (PHs). Although PHs are the best candidates in cell‐based drug screening methods, access to these cells is limited. The application of stem cell–derived hepatocyte‐like cells (HLCs) could overcome these limitations in high‐throughput assessments. However, the functional capacity of HLCs is not enough. Hepatoma cells could be reliable substitutes for PHs and HLCs; however, compared to PHs, their metabolic performance is low. Mimicking the complexity of the liver microenvironment using hepatoma cells and liver‐specific stromal cells in a 3D culture condition represents an innovative, accessible, and scalable platform to accelerate drug development if the metabolic capacity of hepatoma cells is enhanced. This can reduce time, costs, and address the ethical concerns related to animal models and pluripotent stem cells. In this manuscript, we showed that mimicking the complexity of the liver microenvironment in a 3D co‐culture condition with non‐parenchymal cells and improving the metabolic performance of hepatoma cells represents an innovative and accessible platform to accelerate drug discovery and development. Exploring various sources for hepatocytes: Advantages and disadvantages of each source of cells; foundations for advancements in the ADME‐Tox assay.
Recapitulating in vivo conditions of metabolism remains a challenging subject in biomedical research such as ADME-Tox assays (absorption, distribution, metabolism, excretion, and toxicity). The advanced technologies using 3D co-culture methods enabled researchers to develop cell-cell and cell-extracellular matrix (ECM) interactions similar to the natural liver, resulting in the improvement of the metabolic performance of ex vivo cultured primary hepatocytes (PHs). Although PHs are the best candidates in cell-based drug screening methods, access to these cells is limited. The application of stem cell-derived hepatocyte-like cells (HLCs) could overcome these limitations in high-throughput assessments. However, the functional capacity of HLCs is not enough. Hepatoma cells could be reliable substitutes for PHs and HLCs; however, compared to PHs, their metabolic performance is low. Mimicking the complexity of the liver microenvironment using hepatoma cells and liver-specific stromal cells in a 3D culture condition represents an innovative, accessible, and scalable platform to accelerate drug development if the metabolic capacity of hepatoma cells is enhanced. This can reduce time, costs, and address the ethical concerns related to animal models and pluripotent stem cells. In this manuscript, we showed that mimicking the complexity of the liver microenvironment in a 3D co-culture condition with non-parenchymal cells and improving the metabolic performance of hepatoma cells represents an innovative and accessible platform to accelerate drug discovery and development.Recapitulating in vivo conditions of metabolism remains a challenging subject in biomedical research such as ADME-Tox assays (absorption, distribution, metabolism, excretion, and toxicity). The advanced technologies using 3D co-culture methods enabled researchers to develop cell-cell and cell-extracellular matrix (ECM) interactions similar to the natural liver, resulting in the improvement of the metabolic performance of ex vivo cultured primary hepatocytes (PHs). Although PHs are the best candidates in cell-based drug screening methods, access to these cells is limited. The application of stem cell-derived hepatocyte-like cells (HLCs) could overcome these limitations in high-throughput assessments. However, the functional capacity of HLCs is not enough. Hepatoma cells could be reliable substitutes for PHs and HLCs; however, compared to PHs, their metabolic performance is low. Mimicking the complexity of the liver microenvironment using hepatoma cells and liver-specific stromal cells in a 3D culture condition represents an innovative, accessible, and scalable platform to accelerate drug development if the metabolic capacity of hepatoma cells is enhanced. This can reduce time, costs, and address the ethical concerns related to animal models and pluripotent stem cells. In this manuscript, we showed that mimicking the complexity of the liver microenvironment in a 3D co-culture condition with non-parenchymal cells and improving the metabolic performance of hepatoma cells represents an innovative and accessible platform to accelerate drug discovery and development.
ABSTRACT Recapitulating in vivo conditions of metabolism remains a challenging subject in biomedical research such as ADME‐Tox assays (absorption, distribution, metabolism, excretion, and toxicity). The advanced technologies using 3D co‐culture methods enabled researchers to develop cell–cell and cell–extracellular matrix (ECM) interactions similar to the natural liver, resulting in the improvement of the metabolic performance of ex vivo cultured primary hepatocytes (PHs). Although PHs are the best candidates in cell‐based drug screening methods, access to these cells is limited. The application of stem cell–derived hepatocyte‐like cells (HLCs) could overcome these limitations in high‐throughput assessments. However, the functional capacity of HLCs is not enough. Hepatoma cells could be reliable substitutes for PHs and HLCs; however, compared to PHs, their metabolic performance is low. Mimicking the complexity of the liver microenvironment using hepatoma cells and liver‐specific stromal cells in a 3D culture condition represents an innovative, accessible, and scalable platform to accelerate drug development if the metabolic capacity of hepatoma cells is enhanced. This can reduce time, costs, and address the ethical concerns related to animal models and pluripotent stem cells. In this manuscript, we showed that mimicking the complexity of the liver microenvironment in a 3D co‐culture condition with non‐parenchymal cells and improving the metabolic performance of hepatoma cells represents an innovative and accessible platform to accelerate drug discovery and development.
Author Taleahmad, Sara
Shokouhian, Bahare
Najimi, Mustapha
Vosough, Massoud
Hashemian, Zohreh
AuthorAffiliation 3 Department of Stem Cells and Developmental Biology, Cell Science Research Center Royan Institute for Stem Cell Biology and Technology, ACECR Tehran Iran
2 Department of Applied Cell Sciences, Faculty of Basic Sciences and Advanced Medical Technologies Royan Institute, ACECR Tehran Iran
6 Experimental Cancer Medicine Institution for Laboratory Medicine, Karolinska Institute Stockholm Sweden
1 Department of Regenerative Medicine, Cell Science Research Center Royan Institute for Stem Cell Biology and Technology, ACECR Tehran Iran
5 Laboratory of Pediatric Hepatology and Cell Therapy Institute of Experimental and Clinical Research (IREC), UCLouvain Brussels Belgium
4 Department of Medical Biotechnology, School of Advanced Technologies in Medicine Tehran University of Medical Sciences Tehran Iran
AuthorAffiliation_xml – name: 1 Department of Regenerative Medicine, Cell Science Research Center Royan Institute for Stem Cell Biology and Technology, ACECR Tehran Iran
– name: 5 Laboratory of Pediatric Hepatology and Cell Therapy Institute of Experimental and Clinical Research (IREC), UCLouvain Brussels Belgium
– name: 6 Experimental Cancer Medicine Institution for Laboratory Medicine, Karolinska Institute Stockholm Sweden
– name: 2 Department of Applied Cell Sciences, Faculty of Basic Sciences and Advanced Medical Technologies Royan Institute, ACECR Tehran Iran
– name: 3 Department of Stem Cells and Developmental Biology, Cell Science Research Center Royan Institute for Stem Cell Biology and Technology, ACECR Tehran Iran
– name: 4 Department of Medical Biotechnology, School of Advanced Technologies in Medicine Tehran University of Medical Sciences Tehran Iran
Author_xml – sequence: 1
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  surname: Hashemian
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– sequence: 3
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  surname: Shokouhian
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  givenname: Massoud
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  surname: Vosough
  fullname: Vosough, Massoud
  email: masvos@yahoo.com
  organization: Institution for Laboratory Medicine, Karolinska Institute
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Copyright 2025 The Author(s). published by British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics and John Wiley & Sons Ltd.
2025 The Author(s). Pharmacology Research & Perspectives published by British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics and John Wiley & Sons Ltd.
2025. This work is published under http://creativecommons.org/licenses/by/4.0/ (the "License"). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
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– notice: 2025. This work is published under http://creativecommons.org/licenses/by/4.0/ (the "License"). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
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Keywords drug screening platforms
improved metabolic performance
hepatocytes
hepatoma cells
biomedical research
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2017; 120
2010; 3
2018; 33
2021; 9
2023; 13
2021; 4
2019; 6
2013; 87
2023; 15
2023; 16
2017; 22
2023; 209
2022; 42
2024; 12
2024; 15
2024; 19
2022; 237
2016; 11
2022; 188
2021; 13
2021; 10
2021; 12
2022; 2022
2021; 11
2023
2022
2019; 85
2021
2015; 62
2015; 20
2020; 71
2019; 47
2022; 12
2019
2022; 14
2022; 15
2023; 114
2021; 450
2022; 96
2022; 10
2022; 11
2020; 21
2022; 2
2013
2012; 86
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Snippet ABSTRACT Recapitulating in vivo conditions of metabolism remains a challenging subject in biomedical research such as ADME‐Tox assays (absorption,...
Recapitulating in vivo conditions of metabolism remains a challenging subject in biomedical research such as ADME‐Tox assays (absorption, distribution,...
Recapitulating in vivo conditions of metabolism remains a challenging subject in biomedical research such as ADME-Tox assays (absorption, distribution,...
ABSTRACT Recapitulating in vivo conditions of metabolism remains a challenging subject in biomedical research such as ADME‐Tox assays (absorption,...
Recapitulating in vivo conditions of metabolism remains a challenging subject in biomedical research such as ADME-Tox assays (absorption, distribution,...
ABSTRACT Recapitulating in vivo conditions of metabolism remains a challenging subject in biomedical research such as ADME‐Tox assays (absorption,...
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SubjectTerms Animals
biomedical research
Biomedical Research - methods
Carcinoma, Hepatocellular - metabolism
Carcinoma, Hepatocellular - pathology
Coculture Techniques - methods
Drug development
Drug Evaluation, Preclinical - methods
drug screening platforms
hepatocytes
Hepatocytes - cytology
Hepatocytes - metabolism
hepatoma cells
Humans
improved metabolic performance
Liver - cytology
Liver - metabolism
Liver Neoplasms - metabolism
Liver Neoplasms - pathology
Metabolites
Review
Stem cells
Toxicity
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Title Functional Liver Cell–Based Platforms in Biomedical Research
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