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Paracrine Regulation of Alveolar Epithelial Damage and Repair Responses by Human Lung-Resident Mesenchymal Stromal Cells

COPD is characterized by irreversible lung tissue damage. We hypothesized that lung-derived mesenchymal stromal cells (LMSCs) reduce alveolar epithelial damage via paracrine processes, and may thus be suitable for cell-based strategies in COPD. We aimed to assess whether COPD-derived LMSCs display a...

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Autores principales: Kruk, Dennis M. L. W., Wisman, Marissa, Noordhoek, Jacobien A., Nizamoglu, Mehmet, Jonker, Marnix R., de Bruin, Harold G., Arevalo Gomez, Karla, ten Hacken, Nick H. T., Pouwels, Simon D., Heijink, Irene H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8616441/
https://www.ncbi.nlm.nih.gov/pubmed/34831082
http://dx.doi.org/10.3390/cells10112860
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author Kruk, Dennis M. L. W.
Wisman, Marissa
Noordhoek, Jacobien A.
Nizamoglu, Mehmet
Jonker, Marnix R.
de Bruin, Harold G.
Arevalo Gomez, Karla
ten Hacken, Nick H. T.
Pouwels, Simon D.
Heijink, Irene H.
author_facet Kruk, Dennis M. L. W.
Wisman, Marissa
Noordhoek, Jacobien A.
Nizamoglu, Mehmet
Jonker, Marnix R.
de Bruin, Harold G.
Arevalo Gomez, Karla
ten Hacken, Nick H. T.
Pouwels, Simon D.
Heijink, Irene H.
author_sort Kruk, Dennis M. L. W.
collection PubMed
description COPD is characterized by irreversible lung tissue damage. We hypothesized that lung-derived mesenchymal stromal cells (LMSCs) reduce alveolar epithelial damage via paracrine processes, and may thus be suitable for cell-based strategies in COPD. We aimed to assess whether COPD-derived LMSCs display abnormalities. LMSCs were isolated from lung tissue of severe COPD patients and non-COPD controls. Effects of LMSC conditioned-medium (CM) on H(2)O(2)-induced, electric field- and scratch-injury were studied in A549 and NCI-H441 epithelial cells. In organoid models, LMSCs were co-cultured with NCI-H441 or primary lung cells. Organoid number, size and expression of alveolar type II markers were assessed. Pre-treatment with LMSC-CM significantly attenuated oxidative stress-induced necrosis and accelerated wound repair in A549. Co-culture with LMSCs supported organoid formation in NCI-H441 and primary epithelial cells, resulting in significantly larger organoids with lower type II-marker positivity in the presence of COPD-derived versus control LMSCs. Similar abnormalities developed in organoids from COPD compared to control-derived lung cells, with significantly larger organoids. Collectively, this indicates that LMSCs’ secretome attenuates alveolar epithelial injury and supports epithelial repair. Additionally, LMSCs promote generation of alveolar organoids, with abnormalities in the supportive effects of COPD-derived LMCS, reflective of impaired regenerative responses of COPD distal lung cells.
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spelling pubmed-86164412021-11-26 Paracrine Regulation of Alveolar Epithelial Damage and Repair Responses by Human Lung-Resident Mesenchymal Stromal Cells Kruk, Dennis M. L. W. Wisman, Marissa Noordhoek, Jacobien A. Nizamoglu, Mehmet Jonker, Marnix R. de Bruin, Harold G. Arevalo Gomez, Karla ten Hacken, Nick H. T. Pouwels, Simon D. Heijink, Irene H. Cells Article COPD is characterized by irreversible lung tissue damage. We hypothesized that lung-derived mesenchymal stromal cells (LMSCs) reduce alveolar epithelial damage via paracrine processes, and may thus be suitable for cell-based strategies in COPD. We aimed to assess whether COPD-derived LMSCs display abnormalities. LMSCs were isolated from lung tissue of severe COPD patients and non-COPD controls. Effects of LMSC conditioned-medium (CM) on H(2)O(2)-induced, electric field- and scratch-injury were studied in A549 and NCI-H441 epithelial cells. In organoid models, LMSCs were co-cultured with NCI-H441 or primary lung cells. Organoid number, size and expression of alveolar type II markers were assessed. Pre-treatment with LMSC-CM significantly attenuated oxidative stress-induced necrosis and accelerated wound repair in A549. Co-culture with LMSCs supported organoid formation in NCI-H441 and primary epithelial cells, resulting in significantly larger organoids with lower type II-marker positivity in the presence of COPD-derived versus control LMSCs. Similar abnormalities developed in organoids from COPD compared to control-derived lung cells, with significantly larger organoids. Collectively, this indicates that LMSCs’ secretome attenuates alveolar epithelial injury and supports epithelial repair. Additionally, LMSCs promote generation of alveolar organoids, with abnormalities in the supportive effects of COPD-derived LMCS, reflective of impaired regenerative responses of COPD distal lung cells. MDPI 2021-10-23 /pmc/articles/PMC8616441/ /pubmed/34831082 http://dx.doi.org/10.3390/cells10112860 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kruk, Dennis M. L. W.
Wisman, Marissa
Noordhoek, Jacobien A.
Nizamoglu, Mehmet
Jonker, Marnix R.
de Bruin, Harold G.
Arevalo Gomez, Karla
ten Hacken, Nick H. T.
Pouwels, Simon D.
Heijink, Irene H.
Paracrine Regulation of Alveolar Epithelial Damage and Repair Responses by Human Lung-Resident Mesenchymal Stromal Cells
title Paracrine Regulation of Alveolar Epithelial Damage and Repair Responses by Human Lung-Resident Mesenchymal Stromal Cells
title_full Paracrine Regulation of Alveolar Epithelial Damage and Repair Responses by Human Lung-Resident Mesenchymal Stromal Cells
title_fullStr Paracrine Regulation of Alveolar Epithelial Damage and Repair Responses by Human Lung-Resident Mesenchymal Stromal Cells
title_full_unstemmed Paracrine Regulation of Alveolar Epithelial Damage and Repair Responses by Human Lung-Resident Mesenchymal Stromal Cells
title_short Paracrine Regulation of Alveolar Epithelial Damage and Repair Responses by Human Lung-Resident Mesenchymal Stromal Cells
title_sort paracrine regulation of alveolar epithelial damage and repair responses by human lung-resident mesenchymal stromal cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8616441/
https://www.ncbi.nlm.nih.gov/pubmed/34831082
http://dx.doi.org/10.3390/cells10112860
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