SARS-CoV-2 Exposed Mesenchymal Stromal Cell from Congenital Pulmonary Airway Malformations: Transcriptomic Analysis and the Expression of Immunomodulatory Genes

The inflammatory response plays a central role in the complications of congenital pulmonary airway malformations (CPAM) and severe coronavirus disease 2019 (COVID-19). The aim of this study was to evaluate the transcriptional changes induced by SARS-CoV-2 exposure in pediatric MSCs derived from pedi...

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Autores principales:	Andrea Valeri, Luigi Chiricosta, Agnese Gugliandolo, Mara Biasin, Maria Antonietta Avanzini, Valeria Calcaterra, Gioia Cappelletti, Stephana Carelli, Gian Vincenzo Zuccotti, Serena Silvestro, Emanuela Mazzon, Gloria Pelizzo
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	mesenchymal stromal cell congenital pulmonary airway malformations SARS-CoV-2 transcriptomic analysis Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/ecfe1e1cbdbb4ae296289ef6959c7e1b
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spelling	oai:doaj.org-article:ecfe1e1cbdbb4ae296289ef6959c7e1b2021-11-11T17:15:20ZSARS-CoV-2 Exposed Mesenchymal Stromal Cell from Congenital Pulmonary Airway Malformations: Transcriptomic Analysis and the Expression of Immunomodulatory Genes10.3390/ijms2221118141422-00671661-6596https://doaj.org/article/ecfe1e1cbdbb4ae296289ef6959c7e1b2021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11814https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067The inflammatory response plays a central role in the complications of congenital pulmonary airway malformations (CPAM) and severe coronavirus disease 2019 (COVID-19). The aim of this study was to evaluate the transcriptional changes induced by SARS-CoV-2 exposure in pediatric MSCs derived from pediatric lung (MSCs-lung) and CPAM tissues (MSCs-CPAM) in order to elucidate potential pathways involved in SARS-CoV-2 infection in a condition of exacerbated inflammatory response. MSCs-lung and MSCs-CPAM do not express angiotensin-converting enzyme 2 (<i>ACE2</i>) and transmembrane serine protease 2 (<i>TRMPSS2</i>). SARS-CoV-2 appears to be unable to replicate in MSCs-CPAM and MSCs-lung. MSCs-lung and MSCs-CPAM maintained the expression of stemness markers MSCs-lung show an inflammatory response (<i>IL6</i>, <i>IL1B</i>, <i>CXCL8</i>, and <i>CXCL10</i>), and the activation of Notch3 non-canonical pathway; this route appears silent in MSCs-CPAM, and cytokine genes expression is reduced. Decreased value of p21 in MSCs-lung suggested no cell cycle block, and cells did not undergo apoptosis. MSCs-lung appears to increase genes associated with immunomodulatory function but could contribute to inflammation, while MSCs-CPAM keeps stable or reduce the immunomodulatory receptors expression, but they also reduce their cytokines expression. These data indicated that, independently from their perilesional or cystic origin, the MSCs populations already present in a patient affected with CPAM are not permissive for SARS-CoV-2 entry, and they will not spread the disease in case of infection. Moreover, these MSCs will not undergo apoptosis when they come in contact with SARS-CoV-2; on the contrary, they maintain their staminality profile.Andrea ValeriLuigi ChiricostaAgnese GugliandoloMara BiasinMaria Antonietta AvanziniValeria CalcaterraGioia CappellettiStephana CarelliGian Vincenzo ZuccottiSerena SilvestroEmanuela MazzonGloria PelizzoMDPI AGarticlemesenchymal stromal cellcongenital pulmonary airway malformationsSARS-CoV-2transcriptomic analysisBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11814, p 11814 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	mesenchymal stromal cell congenital pulmonary airway malformations SARS-CoV-2 transcriptomic analysis Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	mesenchymal stromal cell congenital pulmonary airway malformations SARS-CoV-2 transcriptomic analysis Biology (General) QH301-705.5 Chemistry QD1-999 Andrea Valeri Luigi Chiricosta Agnese Gugliandolo Mara Biasin Maria Antonietta Avanzini Valeria Calcaterra Gioia Cappelletti Stephana Carelli Gian Vincenzo Zuccotti Serena Silvestro Emanuela Mazzon Gloria Pelizzo SARS-CoV-2 Exposed Mesenchymal Stromal Cell from Congenital Pulmonary Airway Malformations: Transcriptomic Analysis and the Expression of Immunomodulatory Genes
description	The inflammatory response plays a central role in the complications of congenital pulmonary airway malformations (CPAM) and severe coronavirus disease 2019 (COVID-19). The aim of this study was to evaluate the transcriptional changes induced by SARS-CoV-2 exposure in pediatric MSCs derived from pediatric lung (MSCs-lung) and CPAM tissues (MSCs-CPAM) in order to elucidate potential pathways involved in SARS-CoV-2 infection in a condition of exacerbated inflammatory response. MSCs-lung and MSCs-CPAM do not express angiotensin-converting enzyme 2 (<i>ACE2</i>) and transmembrane serine protease 2 (<i>TRMPSS2</i>). SARS-CoV-2 appears to be unable to replicate in MSCs-CPAM and MSCs-lung. MSCs-lung and MSCs-CPAM maintained the expression of stemness markers MSCs-lung show an inflammatory response (<i>IL6</i>, <i>IL1B</i>, <i>CXCL8</i>, and <i>CXCL10</i>), and the activation of Notch3 non-canonical pathway; this route appears silent in MSCs-CPAM, and cytokine genes expression is reduced. Decreased value of p21 in MSCs-lung suggested no cell cycle block, and cells did not undergo apoptosis. MSCs-lung appears to increase genes associated with immunomodulatory function but could contribute to inflammation, while MSCs-CPAM keeps stable or reduce the immunomodulatory receptors expression, but they also reduce their cytokines expression. These data indicated that, independently from their perilesional or cystic origin, the MSCs populations already present in a patient affected with CPAM are not permissive for SARS-CoV-2 entry, and they will not spread the disease in case of infection. Moreover, these MSCs will not undergo apoptosis when they come in contact with SARS-CoV-2; on the contrary, they maintain their staminality profile.
format	article
author	Andrea Valeri Luigi Chiricosta Agnese Gugliandolo Mara Biasin Maria Antonietta Avanzini Valeria Calcaterra Gioia Cappelletti Stephana Carelli Gian Vincenzo Zuccotti Serena Silvestro Emanuela Mazzon Gloria Pelizzo
author_facet	Andrea Valeri Luigi Chiricosta Agnese Gugliandolo Mara Biasin Maria Antonietta Avanzini Valeria Calcaterra Gioia Cappelletti Stephana Carelli Gian Vincenzo Zuccotti Serena Silvestro Emanuela Mazzon Gloria Pelizzo
author_sort	Andrea Valeri
title	SARS-CoV-2 Exposed Mesenchymal Stromal Cell from Congenital Pulmonary Airway Malformations: Transcriptomic Analysis and the Expression of Immunomodulatory Genes
title_short	SARS-CoV-2 Exposed Mesenchymal Stromal Cell from Congenital Pulmonary Airway Malformations: Transcriptomic Analysis and the Expression of Immunomodulatory Genes
title_full	SARS-CoV-2 Exposed Mesenchymal Stromal Cell from Congenital Pulmonary Airway Malformations: Transcriptomic Analysis and the Expression of Immunomodulatory Genes
title_fullStr	SARS-CoV-2 Exposed Mesenchymal Stromal Cell from Congenital Pulmonary Airway Malformations: Transcriptomic Analysis and the Expression of Immunomodulatory Genes
title_full_unstemmed	SARS-CoV-2 Exposed Mesenchymal Stromal Cell from Congenital Pulmonary Airway Malformations: Transcriptomic Analysis and the Expression of Immunomodulatory Genes
title_sort	sars-cov-2 exposed mesenchymal stromal cell from congenital pulmonary airway malformations: transcriptomic analysis and the expression of immunomodulatory genes
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/ecfe1e1cbdbb4ae296289ef6959c7e1b
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SARS-CoV-2 Exposed Mesenchymal Stromal Cell from Congenital Pulmonary Airway Malformations: Transcriptomic Analysis and the Expression of Immunomodulatory Genes

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