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Impact of the Physical Cellular Microenvironment on the Structure and Function of a Model Hepatocyte Cell Line for Drug Toxicity Applications

It is widely recognised that cells respond to their microenvironment, which has implications for cell culture practices. Growth cues provided by 2D cell culture substrates are far removed from native 3D tissue structure in vivo. Geometry is one of many factors that differs between in vitro culture a...

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Autores principales: Allcock, Benjamin, Wei, Wenbin, Goncalves, Kirsty, Hoyle, Henry, Robert, Alisha, Quelch-Cliffe, Rebecca, Hayward, Adam, Cooper, Jim, Przyborski, Stefan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10572302/
https://www.ncbi.nlm.nih.gov/pubmed/37830622
http://dx.doi.org/10.3390/cells12192408
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author Allcock, Benjamin
Wei, Wenbin
Goncalves, Kirsty
Hoyle, Henry
Robert, Alisha
Quelch-Cliffe, Rebecca
Hayward, Adam
Cooper, Jim
Przyborski, Stefan
author_facet Allcock, Benjamin
Wei, Wenbin
Goncalves, Kirsty
Hoyle, Henry
Robert, Alisha
Quelch-Cliffe, Rebecca
Hayward, Adam
Cooper, Jim
Przyborski, Stefan
author_sort Allcock, Benjamin
collection PubMed
description It is widely recognised that cells respond to their microenvironment, which has implications for cell culture practices. Growth cues provided by 2D cell culture substrates are far removed from native 3D tissue structure in vivo. Geometry is one of many factors that differs between in vitro culture and in vivo cellular environments. Cultured cells are far removed from their native counterparts and lose some of their predictive capability and reliability. In this study, we examine the cellular processes that occur when a cell is cultured on 2D or 3D surfaces for a short period of 8 days prior to its use in functional assays, which we term: “priming”. We follow the process of mechanotransduction from cytoskeletal alterations, to changes to nuclear structure, leading to alterations in gene expression, protein expression and improved functional capabilities. In this study, we utilise HepG2 cells as a hepatocyte model cell line, due to their robustness for drug toxicity screening. Here, we demonstrate enhanced functionality and improved drug toxicity profiles that better reflect the in vivo clinical response. However, findings more broadly reflect in vitro cell culture practises across many areas of cell biology, demonstrating the fundamental impact of mechanotransduction in bioengineering and cell biology.
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spelling pubmed-105723022023-10-14 Impact of the Physical Cellular Microenvironment on the Structure and Function of a Model Hepatocyte Cell Line for Drug Toxicity Applications Allcock, Benjamin Wei, Wenbin Goncalves, Kirsty Hoyle, Henry Robert, Alisha Quelch-Cliffe, Rebecca Hayward, Adam Cooper, Jim Przyborski, Stefan Cells Article It is widely recognised that cells respond to their microenvironment, which has implications for cell culture practices. Growth cues provided by 2D cell culture substrates are far removed from native 3D tissue structure in vivo. Geometry is one of many factors that differs between in vitro culture and in vivo cellular environments. Cultured cells are far removed from their native counterparts and lose some of their predictive capability and reliability. In this study, we examine the cellular processes that occur when a cell is cultured on 2D or 3D surfaces for a short period of 8 days prior to its use in functional assays, which we term: “priming”. We follow the process of mechanotransduction from cytoskeletal alterations, to changes to nuclear structure, leading to alterations in gene expression, protein expression and improved functional capabilities. In this study, we utilise HepG2 cells as a hepatocyte model cell line, due to their robustness for drug toxicity screening. Here, we demonstrate enhanced functionality and improved drug toxicity profiles that better reflect the in vivo clinical response. However, findings more broadly reflect in vitro cell culture practises across many areas of cell biology, demonstrating the fundamental impact of mechanotransduction in bioengineering and cell biology. MDPI 2023-10-05 /pmc/articles/PMC10572302/ /pubmed/37830622 http://dx.doi.org/10.3390/cells12192408 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Allcock, Benjamin
Wei, Wenbin
Goncalves, Kirsty
Hoyle, Henry
Robert, Alisha
Quelch-Cliffe, Rebecca
Hayward, Adam
Cooper, Jim
Przyborski, Stefan
Impact of the Physical Cellular Microenvironment on the Structure and Function of a Model Hepatocyte Cell Line for Drug Toxicity Applications
title Impact of the Physical Cellular Microenvironment on the Structure and Function of a Model Hepatocyte Cell Line for Drug Toxicity Applications
title_full Impact of the Physical Cellular Microenvironment on the Structure and Function of a Model Hepatocyte Cell Line for Drug Toxicity Applications
title_fullStr Impact of the Physical Cellular Microenvironment on the Structure and Function of a Model Hepatocyte Cell Line for Drug Toxicity Applications
title_full_unstemmed Impact of the Physical Cellular Microenvironment on the Structure and Function of a Model Hepatocyte Cell Line for Drug Toxicity Applications
title_short Impact of the Physical Cellular Microenvironment on the Structure and Function of a Model Hepatocyte Cell Line for Drug Toxicity Applications
title_sort impact of the physical cellular microenvironment on the structure and function of a model hepatocyte cell line for drug toxicity applications
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10572302/
https://www.ncbi.nlm.nih.gov/pubmed/37830622
http://dx.doi.org/10.3390/cells12192408
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