The response of three-dimensional pancreatic alpha and beta cell co-cultures to oxidative stress

The pancreatic islets of Langerhans have low endogenous antioxidant levels and are thus especially sensitive to oxidative stress, which is known to influence cell survival and behaviour. As bioengineered islets are gaining interest for therapeutic purposes, it is important to understand how their co...

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Main Authors: Mireille M. J. P. E. Sthijns, Timo Rademakers, Jolien Oosterveer, Thomas Geuens, Clemens A. van Blitterswijk, Vanessa L. S. LaPointe
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2022-01-01
Series:PLoS ONE
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8923503/?tool=EBI
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author Mireille M. J. P. E. Sthijns
Timo Rademakers
Jolien Oosterveer
Thomas Geuens
Clemens A. van Blitterswijk
Vanessa L. S. LaPointe
author_facet Mireille M. J. P. E. Sthijns
Timo Rademakers
Jolien Oosterveer
Thomas Geuens
Clemens A. van Blitterswijk
Vanessa L. S. LaPointe
author_sort Mireille M. J. P. E. Sthijns
collection DOAJ
description The pancreatic islets of Langerhans have low endogenous antioxidant levels and are thus especially sensitive to oxidative stress, which is known to influence cell survival and behaviour. As bioengineered islets are gaining interest for therapeutic purposes, it is important to understand how their composition can be optimized to diminish oxidative stress. We investigated how the ratio of the two main islet cell types (alpha and beta cells) and their culture in three-dimensional aggregates could protect against oxidative stress. Monolayer and aggregate cultures were established by seeding the alphaTC1 (alpha) and INS1E (beta) cell lines in varying ratios, and hydrogen peroxide was applied to induce oxidative stress. Viability, oxidative stress, and the level of the antioxidant glutathione were measured. Both aggregation and an increasing prevalence of INS1E cells in the co-cultures conferred greater resistance to cell death induced by oxidative stress. Increasing the prevalence of INS1E cells also decreased the number of alphaTC1 cells experiencing oxidative stress in the monolayer culture. In 3D aggregates, culturing the alphaTC1 and INS1E cells in a ratio of 50:50 prevented oxidative stress in both cell types. Together, the results of this study lead to new insight into how modulating the composition and dimensionality of a co-culture can influence the oxidative stress levels experienced by the cells.
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spelling doaj.art-24f7acadbc55416fa2a8e80a8e85d0912022-12-21T19:23:36ZengPublic Library of Science (PLoS)PLoS ONE1932-62032022-01-01173The response of three-dimensional pancreatic alpha and beta cell co-cultures to oxidative stressMireille M. J. P. E. SthijnsTimo RademakersJolien OosterveerThomas GeuensClemens A. van BlitterswijkVanessa L. S. LaPointeThe pancreatic islets of Langerhans have low endogenous antioxidant levels and are thus especially sensitive to oxidative stress, which is known to influence cell survival and behaviour. As bioengineered islets are gaining interest for therapeutic purposes, it is important to understand how their composition can be optimized to diminish oxidative stress. We investigated how the ratio of the two main islet cell types (alpha and beta cells) and their culture in three-dimensional aggregates could protect against oxidative stress. Monolayer and aggregate cultures were established by seeding the alphaTC1 (alpha) and INS1E (beta) cell lines in varying ratios, and hydrogen peroxide was applied to induce oxidative stress. Viability, oxidative stress, and the level of the antioxidant glutathione were measured. Both aggregation and an increasing prevalence of INS1E cells in the co-cultures conferred greater resistance to cell death induced by oxidative stress. Increasing the prevalence of INS1E cells also decreased the number of alphaTC1 cells experiencing oxidative stress in the monolayer culture. In 3D aggregates, culturing the alphaTC1 and INS1E cells in a ratio of 50:50 prevented oxidative stress in both cell types. Together, the results of this study lead to new insight into how modulating the composition and dimensionality of a co-culture can influence the oxidative stress levels experienced by the cells.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8923503/?tool=EBI
spellingShingle Mireille M. J. P. E. Sthijns
Timo Rademakers
Jolien Oosterveer
Thomas Geuens
Clemens A. van Blitterswijk
Vanessa L. S. LaPointe
The response of three-dimensional pancreatic alpha and beta cell co-cultures to oxidative stress
PLoS ONE
title The response of three-dimensional pancreatic alpha and beta cell co-cultures to oxidative stress
title_full The response of three-dimensional pancreatic alpha and beta cell co-cultures to oxidative stress
title_fullStr The response of three-dimensional pancreatic alpha and beta cell co-cultures to oxidative stress
title_full_unstemmed The response of three-dimensional pancreatic alpha and beta cell co-cultures to oxidative stress
title_short The response of three-dimensional pancreatic alpha and beta cell co-cultures to oxidative stress
title_sort response of three dimensional pancreatic alpha and beta cell co cultures to oxidative stress
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8923503/?tool=EBI
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