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Spheroid Size Does not Impact Metabolism of the β-blocker Propranolol in 3D Intestinal Fish Model

Compared to two-dimensional (2D) cell culture, cellular aggregates or spheroids (3D) offer a more appropriate alternative in vitro system where individual cell-cell communication and micro-environment more closely represent the in vivo organ; yet we understand little of the physiological conditions...

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Autores principales: Langan, Laura M., Owen, Stewart F., Trznadel, Maciej, Dodd, Nicholas J. F., Jackson, Simon K., Purcell, Wendy M., Jha, Awadhesh N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6113889/
https://www.ncbi.nlm.nih.gov/pubmed/30186177
http://dx.doi.org/10.3389/fphar.2018.00947
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author Langan, Laura M.
Owen, Stewart F.
Trznadel, Maciej
Dodd, Nicholas J. F.
Jackson, Simon K.
Purcell, Wendy M.
Jha, Awadhesh N.
author_facet Langan, Laura M.
Owen, Stewart F.
Trznadel, Maciej
Dodd, Nicholas J. F.
Jackson, Simon K.
Purcell, Wendy M.
Jha, Awadhesh N.
author_sort Langan, Laura M.
collection PubMed
description Compared to two-dimensional (2D) cell culture, cellular aggregates or spheroids (3D) offer a more appropriate alternative in vitro system where individual cell-cell communication and micro-environment more closely represent the in vivo organ; yet we understand little of the physiological conditions at this scale. The relationship between spheroid size and oxygen microenvironment, an important factor influencing the metabolic capacity of cells, was first established using the fish intestine derived RTgutGC cell line. Subsequently, pharmaceutical metabolism (Propranolol), as determined by high performance liquid chromatography, in this intestinal model was examined as a function of spheroid size. Co-efficient of variation between spheroid size was below 12% using the gyratory platform method, with the least variation observed in the highest cell seeding density. The viable, high oxygen micro-environment of the outer rim of the spheroid, as determined by electron paramagnetic resonance (EPR) oximetry, decreased over time, and the hypoxic zone increased as a function of spheroid size. Despite a trend of higher metabolism in smaller spheroids, the formation of micro-environments (quiescent, hypoxic or anoxic) did not significantly affect metabolism or function of an environmentally relevant pharmaceutical in this spheroid model.
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spelling pubmed-61138892018-09-05 Spheroid Size Does not Impact Metabolism of the β-blocker Propranolol in 3D Intestinal Fish Model Langan, Laura M. Owen, Stewart F. Trznadel, Maciej Dodd, Nicholas J. F. Jackson, Simon K. Purcell, Wendy M. Jha, Awadhesh N. Front Pharmacol Pharmacology Compared to two-dimensional (2D) cell culture, cellular aggregates or spheroids (3D) offer a more appropriate alternative in vitro system where individual cell-cell communication and micro-environment more closely represent the in vivo organ; yet we understand little of the physiological conditions at this scale. The relationship between spheroid size and oxygen microenvironment, an important factor influencing the metabolic capacity of cells, was first established using the fish intestine derived RTgutGC cell line. Subsequently, pharmaceutical metabolism (Propranolol), as determined by high performance liquid chromatography, in this intestinal model was examined as a function of spheroid size. Co-efficient of variation between spheroid size was below 12% using the gyratory platform method, with the least variation observed in the highest cell seeding density. The viable, high oxygen micro-environment of the outer rim of the spheroid, as determined by electron paramagnetic resonance (EPR) oximetry, decreased over time, and the hypoxic zone increased as a function of spheroid size. Despite a trend of higher metabolism in smaller spheroids, the formation of micro-environments (quiescent, hypoxic or anoxic) did not significantly affect metabolism or function of an environmentally relevant pharmaceutical in this spheroid model. Frontiers Media S.A. 2018-08-22 /pmc/articles/PMC6113889/ /pubmed/30186177 http://dx.doi.org/10.3389/fphar.2018.00947 Text en Copyright © 2018 Langan, Owen, Trznadel, Dodd, Jackson, Purcell and Jha. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Langan, Laura M.
Owen, Stewart F.
Trznadel, Maciej
Dodd, Nicholas J. F.
Jackson, Simon K.
Purcell, Wendy M.
Jha, Awadhesh N.
Spheroid Size Does not Impact Metabolism of the β-blocker Propranolol in 3D Intestinal Fish Model
title Spheroid Size Does not Impact Metabolism of the β-blocker Propranolol in 3D Intestinal Fish Model
title_full Spheroid Size Does not Impact Metabolism of the β-blocker Propranolol in 3D Intestinal Fish Model
title_fullStr Spheroid Size Does not Impact Metabolism of the β-blocker Propranolol in 3D Intestinal Fish Model
title_full_unstemmed Spheroid Size Does not Impact Metabolism of the β-blocker Propranolol in 3D Intestinal Fish Model
title_short Spheroid Size Does not Impact Metabolism of the β-blocker Propranolol in 3D Intestinal Fish Model
title_sort spheroid size does not impact metabolism of the β-blocker propranolol in 3d intestinal fish model
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6113889/
https://www.ncbi.nlm.nih.gov/pubmed/30186177
http://dx.doi.org/10.3389/fphar.2018.00947
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