{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T02:28:27Z","timestamp":1760236107580,"version":"build-2065373602"},"reference-count":70,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2021,10,30]],"date-time":"2021-10-30T00:00:00Z","timestamp":1635552000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["Current Research Funds 2021"],"award-info":[{"award-number":["Current Research Funds 2021"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Bando Regione Lombardia DG Welfare","award":["RL_DG-WEL20MBIAS_01"],"award-info":[{"award-number":["RL_DG-WEL20MBIAS_01"]}]},{"DOI":"10.13039\/501100002803","name":"Fondazione Cariplo","doi-asserted-by":"publisher","award":["CAR_EXT20MBIAS_01"],"award-info":[{"award-number":["CAR_EXT20MBIAS_01"]}],"id":[{"id":"10.13039\/501100002803","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Fondo integrativo Speciale per la Ricerca Covid-19, Ministero dell'Universit\u00e0 e della Ricerca","award":["FISR2020IP_02959"],"award-info":[{"award-number":["FISR2020IP_02959"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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 (ACE2) and transmembrane serine protease 2 (TRMPSS2). 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 (IL6, IL1B, CXCL8, and CXCL10), 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.<\/jats:p>","DOI":"10.3390\/ijms222111814","type":"journal-article","created":{"date-parts":[[2021,11,1]],"date-time":"2021-11-01T22:21:34Z","timestamp":1635805294000},"page":"11814","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["SARS-CoV-2 Exposed Mesenchymal Stromal Cell from Congenital Pulmonary Airway Malformations: Transcriptomic Analysis and the Expression of Immunomodulatory Genes"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1457-1619","authenticated-orcid":false,"given":"Andrea","family":"Valeri","sequence":"first","affiliation":[{"name":"IRCCS Centro Neurolesi \u201cBonino-Pulejo\u201d, Via Provinciale Palermo, Contrada Casazza, 98124 Messina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0358-7348","authenticated-orcid":false,"given":"Luigi","family":"Chiricosta","sequence":"additional","affiliation":[{"name":"IRCCS Centro Neurolesi \u201cBonino-Pulejo\u201d, Via Provinciale Palermo, Contrada Casazza, 98124 Messina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7868-3353","authenticated-orcid":false,"given":"Agnese","family":"Gugliandolo","sequence":"additional","affiliation":[{"name":"IRCCS Centro Neurolesi \u201cBonino-Pulejo\u201d, Via Provinciale Palermo, Contrada Casazza, 98124 Messina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3671-4235","authenticated-orcid":false,"given":"Mara","family":"Biasin","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Clinical Sciences-L. Sacco, University of Milan, 20157 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6056-9018","authenticated-orcid":false,"given":"Maria Antonietta","family":"Avanzini","sequence":"additional","affiliation":[{"name":"Cell Factory, Pediatric Hematology Oncology Unit, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2137-5974","authenticated-orcid":false,"given":"Valeria","family":"Calcaterra","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Children\u2019s Hospital \u201cVittore Buzzi\u201d, 20154 Milano, Italy"},{"name":"Pediatrics and Adolescentology Unit, Department of Internal Medicine, University of Pavia, 27100 Pavia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2932-2391","authenticated-orcid":false,"given":"Gioia","family":"Cappelletti","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Clinical Sciences-L. Sacco, University of Milan, 20157 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4603-396X","authenticated-orcid":false,"given":"Stephana","family":"Carelli","sequence":"additional","affiliation":[{"name":"Pediatric Clinical Research Center, Fondazione Romeo ed Enrica Invernizzi, University of Milan, 20157 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2795-9874","authenticated-orcid":false,"given":"Gian Vincenzo","family":"Zuccotti","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Clinical Sciences-L. Sacco, University of Milan, 20157 Milan, Italy"},{"name":"Department of Pediatrics, Children\u2019s Hospital \u201cVittore Buzzi\u201d, 20154 Milano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3846-0785","authenticated-orcid":false,"given":"Serena","family":"Silvestro","sequence":"additional","affiliation":[{"name":"IRCCS Centro Neurolesi \u201cBonino-Pulejo\u201d, Via Provinciale Palermo, Contrada Casazza, 98124 Messina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emanuela","family":"Mazzon","sequence":"additional","affiliation":[{"name":"IRCCS Centro Neurolesi \u201cBonino-Pulejo\u201d, Via Provinciale Palermo, Contrada Casazza, 98124 Messina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gloria","family":"Pelizzo","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Clinical Sciences-L. Sacco, University of Milan, 20157 Milan, Italy"},{"name":"Pediatric Surgery Department, Children\u2019s Hospital \u201cVittore Buzzi\u201d, 20154 Milano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,30]]},"reference":[{"key":"ref_1","first-page":"e7423","article-title":"Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2): An Update","volume":"12","author":"Pal","year":"2020","journal-title":"Cureus"},{"key":"ref_2","first-page":"n436","article-title":"Severe covid-19 pneumonia: Pathogenesis and clinical management","volume":"372","author":"Attaway","year":"2021","journal-title":"BMJ Clin. Res. 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