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...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Dennis M. L. W. Kruk, Marissa Wisman, Jacobien A. Noordhoek, Mehmet Nizamoglu, Marnix R. Jonker, Harold G. de Bruin, Karla Arevalo Gomez, Nick H. T. ten Hacken, Simon D. Pouwels, Irene H. Heijink
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	COPD emphysema cell therapy lung repair MSCs alveolar epithelium Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/c260538f10634f8fb47eb09a8a7cee22
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:c260538f10634f8fb47eb09a8a7cee22
record_format	dspace
spelling	oai:doaj.org-article:c260538f10634f8fb47eb09a8a7cee222021-11-25T17:08:09ZParacrine Regulation of Alveolar Epithelial Damage and Repair Responses by Human Lung-Resident Mesenchymal Stromal Cells10.3390/cells101128602073-4409https://doaj.org/article/c260538f10634f8fb47eb09a8a7cee222021-10-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/2860https://doaj.org/toc/2073-4409COPD 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<sub>2</sub>O<sub>2</sub>-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.Dennis M. L. W. KrukMarissa WismanJacobien A. NoordhoekMehmet NizamogluMarnix R. JonkerHarold G. de BruinKarla Arevalo GomezNick H. T. ten HackenSimon D. PouwelsIrene H. HeijinkMDPI AGarticleCOPDemphysemacell therapylung repairMSCsalveolar epitheliumBiology (General)QH301-705.5ENCells, Vol 10, Iss 2860, p 2860 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	COPD emphysema cell therapy lung repair MSCs alveolar epithelium Biology (General) QH301-705.5
spellingShingle	COPD emphysema cell therapy lung repair MSCs alveolar epithelium Biology (General) QH301-705.5 Dennis M. L. W. Kruk Marissa Wisman Jacobien A. Noordhoek Mehmet Nizamoglu Marnix R. Jonker Harold G. de Bruin Karla Arevalo Gomez Nick H. T. ten Hacken Simon D. Pouwels Irene H. Heijink Paracrine Regulation of Alveolar Epithelial Damage and Repair Responses by Human Lung-Resident Mesenchymal Stromal Cells
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<sub>2</sub>O<sub>2</sub>-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.
format	article
author	Dennis M. L. W. Kruk Marissa Wisman Jacobien A. Noordhoek Mehmet Nizamoglu Marnix R. Jonker Harold G. de Bruin Karla Arevalo Gomez Nick H. T. ten Hacken Simon D. Pouwels Irene H. Heijink
author_facet	Dennis M. L. W. Kruk Marissa Wisman Jacobien A. Noordhoek Mehmet Nizamoglu Marnix R. Jonker Harold G. de Bruin Karla Arevalo Gomez Nick H. T. ten Hacken Simon D. Pouwels Irene H. Heijink
author_sort	Dennis M. L. W. Kruk
title	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_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_sort	paracrine regulation of alveolar epithelial damage and repair responses by human lung-resident mesenchymal stromal cells
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/c260538f10634f8fb47eb09a8a7cee22
work_keys_str_mv	AT dennismlwkruk paracrineregulationofalveolarepithelialdamageandrepairresponsesbyhumanlungresidentmesenchymalstromalcells AT marissawisman paracrineregulationofalveolarepithelialdamageandrepairresponsesbyhumanlungresidentmesenchymalstromalcells AT jacobienanoordhoek paracrineregulationofalveolarepithelialdamageandrepairresponsesbyhumanlungresidentmesenchymalstromalcells AT mehmetnizamoglu paracrineregulationofalveolarepithelialdamageandrepairresponsesbyhumanlungresidentmesenchymalstromalcells AT marnixrjonker paracrineregulationofalveolarepithelialdamageandrepairresponsesbyhumanlungresidentmesenchymalstromalcells AT haroldgdebruin paracrineregulationofalveolarepithelialdamageandrepairresponsesbyhumanlungresidentmesenchymalstromalcells AT karlaarevalogomez paracrineregulationofalveolarepithelialdamageandrepairresponsesbyhumanlungresidentmesenchymalstromalcells AT nickhttenhacken paracrineregulationofalveolarepithelialdamageandrepairresponsesbyhumanlungresidentmesenchymalstromalcells AT simondpouwels paracrineregulationofalveolarepithelialdamageandrepairresponsesbyhumanlungresidentmesenchymalstromalcells AT irenehheijink paracrineregulationofalveolarepithelialdamageandrepairresponsesbyhumanlungresidentmesenchymalstromalcells
_version_	1718412739921051648

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

Ejemplares similares