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In Silico Models for Dynamic Connected Cell Cultures Mimicking Hepatocyte-Endothelial Cell-Adipocyte Interaction Circle

The biochemistry of a system made up of three kinds of cell is virtually impossible to work out without the use of in silico models. Here, we deal with homeostatic balance phenomena from a metabolic point of view and we present a new computational model merging three single-cell models, already avai...

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Autores principales: Andreoni, Chiara, Orsi, Gianni, De Maria, Carmelo, Montemurro, Francesca, Vozzi, Giovanni
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4266517/
https://www.ncbi.nlm.nih.gov/pubmed/25502576
http://dx.doi.org/10.1371/journal.pone.0111946
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author Andreoni, Chiara
Orsi, Gianni
De Maria, Carmelo
Montemurro, Francesca
Vozzi, Giovanni
author_facet Andreoni, Chiara
Orsi, Gianni
De Maria, Carmelo
Montemurro, Francesca
Vozzi, Giovanni
author_sort Andreoni, Chiara
collection PubMed
description The biochemistry of a system made up of three kinds of cell is virtually impossible to work out without the use of in silico models. Here, we deal with homeostatic balance phenomena from a metabolic point of view and we present a new computational model merging three single-cell models, already available from our research group: the first model reproduced the metabolic behaviour of a hepatocyte, the second one represented an endothelial cell, and the third one described an adipocyte. Multiple interconnections were created among these three models in order to mimic the main physiological interactions that are known for the examined cell phenotypes. The ultimate aim was to recreate the accomplishment of the homeostatic balance as it was observed for an in vitro connected three-culture system concerning glucose and lipid metabolism in the presence of the medium flow. The whole model was based on a modular approach and on a set of nonlinear differential equations implemented in Simulink, applying Michaelis-Menten kinetic laws and some energy balance considerations to the studied metabolic pathways. Our in silico model was then validated against experimental datasets coming from literature about the cited in vitro model. The agreement between simulated and experimental results was good and the behaviour of the connected culture system was reproduced through an adequate parameter evaluation. The developed model may help other researchers to investigate further about integrated metabolism and the regulation mechanisms underlying the physiological homeostasis.
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spelling pubmed-42665172014-12-26 In Silico Models for Dynamic Connected Cell Cultures Mimicking Hepatocyte-Endothelial Cell-Adipocyte Interaction Circle Andreoni, Chiara Orsi, Gianni De Maria, Carmelo Montemurro, Francesca Vozzi, Giovanni PLoS One Research Article The biochemistry of a system made up of three kinds of cell is virtually impossible to work out without the use of in silico models. Here, we deal with homeostatic balance phenomena from a metabolic point of view and we present a new computational model merging three single-cell models, already available from our research group: the first model reproduced the metabolic behaviour of a hepatocyte, the second one represented an endothelial cell, and the third one described an adipocyte. Multiple interconnections were created among these three models in order to mimic the main physiological interactions that are known for the examined cell phenotypes. The ultimate aim was to recreate the accomplishment of the homeostatic balance as it was observed for an in vitro connected three-culture system concerning glucose and lipid metabolism in the presence of the medium flow. The whole model was based on a modular approach and on a set of nonlinear differential equations implemented in Simulink, applying Michaelis-Menten kinetic laws and some energy balance considerations to the studied metabolic pathways. Our in silico model was then validated against experimental datasets coming from literature about the cited in vitro model. The agreement between simulated and experimental results was good and the behaviour of the connected culture system was reproduced through an adequate parameter evaluation. The developed model may help other researchers to investigate further about integrated metabolism and the regulation mechanisms underlying the physiological homeostasis. Public Library of Science 2014-12-15 /pmc/articles/PMC4266517/ /pubmed/25502576 http://dx.doi.org/10.1371/journal.pone.0111946 Text en © 2014 Andreoni et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Andreoni, Chiara
Orsi, Gianni
De Maria, Carmelo
Montemurro, Francesca
Vozzi, Giovanni
In Silico Models for Dynamic Connected Cell Cultures Mimicking Hepatocyte-Endothelial Cell-Adipocyte Interaction Circle
title In Silico Models for Dynamic Connected Cell Cultures Mimicking Hepatocyte-Endothelial Cell-Adipocyte Interaction Circle
title_full In Silico Models for Dynamic Connected Cell Cultures Mimicking Hepatocyte-Endothelial Cell-Adipocyte Interaction Circle
title_fullStr In Silico Models for Dynamic Connected Cell Cultures Mimicking Hepatocyte-Endothelial Cell-Adipocyte Interaction Circle
title_full_unstemmed In Silico Models for Dynamic Connected Cell Cultures Mimicking Hepatocyte-Endothelial Cell-Adipocyte Interaction Circle
title_short In Silico Models for Dynamic Connected Cell Cultures Mimicking Hepatocyte-Endothelial Cell-Adipocyte Interaction Circle
title_sort in silico models for dynamic connected cell cultures mimicking hepatocyte-endothelial cell-adipocyte interaction circle
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4266517/
https://www.ncbi.nlm.nih.gov/pubmed/25502576
http://dx.doi.org/10.1371/journal.pone.0111946
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