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Mesenchymal stromal cell aging impairs the self-organizing capacity of lung alveolar epithelial stem cells

Multicellular organisms maintain structure and function of tissues/organs through emergent, self-organizing behavior. In this report, we demonstrate a critical role for lung mesenchymal stromal cell (L-MSC) aging in determining the capacity to form three-dimensional organoids or ‘alveolospheres’ wit...

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Autores principales: Chanda, Diptiman, Rehan, Mohammad, Smith, Samuel R, Dsouza, Kevin G, Wang, Yong, Bernard, Karen, Kurundkar, Deepali, Memula, Vinayak, Kojima, Kyoko, Mobley, James A, Benavides, Gloria A, Darley-Usmar, Victor, Kim, Young-iL, Zmijewski, Jaroslaw W, Deshane, Jessy S, De Langhe, Stijn, Thannickal, Victor J
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8445616/
https://www.ncbi.nlm.nih.gov/pubmed/34528872
http://dx.doi.org/10.7554/eLife.68049
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author Chanda, Diptiman
Rehan, Mohammad
Smith, Samuel R
Dsouza, Kevin G
Wang, Yong
Bernard, Karen
Kurundkar, Deepali
Memula, Vinayak
Kojima, Kyoko
Mobley, James A
Benavides, Gloria A
Darley-Usmar, Victor
Kim, Young-iL
Zmijewski, Jaroslaw W
Deshane, Jessy S
De Langhe, Stijn
Thannickal, Victor J
author_facet Chanda, Diptiman
Rehan, Mohammad
Smith, Samuel R
Dsouza, Kevin G
Wang, Yong
Bernard, Karen
Kurundkar, Deepali
Memula, Vinayak
Kojima, Kyoko
Mobley, James A
Benavides, Gloria A
Darley-Usmar, Victor
Kim, Young-iL
Zmijewski, Jaroslaw W
Deshane, Jessy S
De Langhe, Stijn
Thannickal, Victor J
author_sort Chanda, Diptiman
collection PubMed
description Multicellular organisms maintain structure and function of tissues/organs through emergent, self-organizing behavior. In this report, we demonstrate a critical role for lung mesenchymal stromal cell (L-MSC) aging in determining the capacity to form three-dimensional organoids or ‘alveolospheres’ with type 2 alveolar epithelial cells (AEC2s). In contrast to L-MSCs from aged mice, young L-MSCs support the efficient formation of alveolospheres when co-cultured with young or aged AEC2s. Aged L-MSCs demonstrated features of cellular senescence, altered bioenergetics, and a senescence-associated secretory profile (SASP). The reactive oxygen species generating enzyme, NADPH oxidase 4 (Nox4), was highly activated in aged L-MSCs and Nox4 downregulation was sufficient to, at least partially, reverse this age-related energy deficit, while restoring the self-organizing capacity of alveolospheres. Together, these data indicate a critical role for cellular bioenergetics and redox homeostasis in an organoid model of self-organization and support the concept of thermodynamic entropy in aging biology.
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spelling pubmed-84456162021-09-17 Mesenchymal stromal cell aging impairs the self-organizing capacity of lung alveolar epithelial stem cells Chanda, Diptiman Rehan, Mohammad Smith, Samuel R Dsouza, Kevin G Wang, Yong Bernard, Karen Kurundkar, Deepali Memula, Vinayak Kojima, Kyoko Mobley, James A Benavides, Gloria A Darley-Usmar, Victor Kim, Young-iL Zmijewski, Jaroslaw W Deshane, Jessy S De Langhe, Stijn Thannickal, Victor J eLife Stem Cells and Regenerative Medicine Multicellular organisms maintain structure and function of tissues/organs through emergent, self-organizing behavior. In this report, we demonstrate a critical role for lung mesenchymal stromal cell (L-MSC) aging in determining the capacity to form three-dimensional organoids or ‘alveolospheres’ with type 2 alveolar epithelial cells (AEC2s). In contrast to L-MSCs from aged mice, young L-MSCs support the efficient formation of alveolospheres when co-cultured with young or aged AEC2s. Aged L-MSCs demonstrated features of cellular senescence, altered bioenergetics, and a senescence-associated secretory profile (SASP). The reactive oxygen species generating enzyme, NADPH oxidase 4 (Nox4), was highly activated in aged L-MSCs and Nox4 downregulation was sufficient to, at least partially, reverse this age-related energy deficit, while restoring the self-organizing capacity of alveolospheres. Together, these data indicate a critical role for cellular bioenergetics and redox homeostasis in an organoid model of self-organization and support the concept of thermodynamic entropy in aging biology. eLife Sciences Publications, Ltd 2021-09-16 /pmc/articles/PMC8445616/ /pubmed/34528872 http://dx.doi.org/10.7554/eLife.68049 Text en © 2021, Chanda et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Stem Cells and Regenerative Medicine
Chanda, Diptiman
Rehan, Mohammad
Smith, Samuel R
Dsouza, Kevin G
Wang, Yong
Bernard, Karen
Kurundkar, Deepali
Memula, Vinayak
Kojima, Kyoko
Mobley, James A
Benavides, Gloria A
Darley-Usmar, Victor
Kim, Young-iL
Zmijewski, Jaroslaw W
Deshane, Jessy S
De Langhe, Stijn
Thannickal, Victor J
Mesenchymal stromal cell aging impairs the self-organizing capacity of lung alveolar epithelial stem cells
title Mesenchymal stromal cell aging impairs the self-organizing capacity of lung alveolar epithelial stem cells
title_full Mesenchymal stromal cell aging impairs the self-organizing capacity of lung alveolar epithelial stem cells
title_fullStr Mesenchymal stromal cell aging impairs the self-organizing capacity of lung alveolar epithelial stem cells
title_full_unstemmed Mesenchymal stromal cell aging impairs the self-organizing capacity of lung alveolar epithelial stem cells
title_short Mesenchymal stromal cell aging impairs the self-organizing capacity of lung alveolar epithelial stem cells
title_sort mesenchymal stromal cell aging impairs the self-organizing capacity of lung alveolar epithelial stem cells
topic Stem Cells and Regenerative Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8445616/
https://www.ncbi.nlm.nih.gov/pubmed/34528872
http://dx.doi.org/10.7554/eLife.68049
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