Cargando…
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...
Autores principales: | , , , , , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1784568688065642496 |
---|---|
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. |
format | Online Article Text |
id | pubmed-8445616 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT chandadiptiman mesenchymalstromalcellagingimpairstheselforganizingcapacityoflungalveolarepithelialstemcells AT rehanmohammad mesenchymalstromalcellagingimpairstheselforganizingcapacityoflungalveolarepithelialstemcells AT smithsamuelr mesenchymalstromalcellagingimpairstheselforganizingcapacityoflungalveolarepithelialstemcells AT dsouzakeving mesenchymalstromalcellagingimpairstheselforganizingcapacityoflungalveolarepithelialstemcells AT wangyong mesenchymalstromalcellagingimpairstheselforganizingcapacityoflungalveolarepithelialstemcells AT bernardkaren mesenchymalstromalcellagingimpairstheselforganizingcapacityoflungalveolarepithelialstemcells AT kurundkardeepali mesenchymalstromalcellagingimpairstheselforganizingcapacityoflungalveolarepithelialstemcells AT memulavinayak mesenchymalstromalcellagingimpairstheselforganizingcapacityoflungalveolarepithelialstemcells AT kojimakyoko mesenchymalstromalcellagingimpairstheselforganizingcapacityoflungalveolarepithelialstemcells AT mobleyjamesa mesenchymalstromalcellagingimpairstheselforganizingcapacityoflungalveolarepithelialstemcells AT benavidesgloriaa mesenchymalstromalcellagingimpairstheselforganizingcapacityoflungalveolarepithelialstemcells AT darleyusmarvictor mesenchymalstromalcellagingimpairstheselforganizingcapacityoflungalveolarepithelialstemcells AT kimyoungil mesenchymalstromalcellagingimpairstheselforganizingcapacityoflungalveolarepithelialstemcells AT zmijewskijaroslaww mesenchymalstromalcellagingimpairstheselforganizingcapacityoflungalveolarepithelialstemcells AT deshanejessys mesenchymalstromalcellagingimpairstheselforganizingcapacityoflungalveolarepithelialstemcells AT delanghestijn mesenchymalstromalcellagingimpairstheselforganizingcapacityoflungalveolarepithelialstemcells AT thannickalvictorj mesenchymalstromalcellagingimpairstheselforganizingcapacityoflungalveolarepithelialstemcells |