{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T08:08:59Z","timestamp":1776326939084,"version":"3.50.1"},"reference-count":39,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2024,3,1]],"date-time":"2024-03-01T00:00:00Z","timestamp":1709251200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Euratom research and training program 2014\u20132018","award":["N. 755523"],"award-info":[{"award-number":["N. 755523"]}]},{"name":"Euratom research and training program 2014\u20132018","award":["# RM12117A805ED2FD"],"award-info":[{"award-number":["# RM12117A805ED2FD"]}]},{"name":"Euratom research and training program 2014\u20132018","award":["Progetto ECS 0000024 Rome Technopole"],"award-info":[{"award-number":["Progetto ECS 0000024 Rome Technopole"]}]},{"name":"Euratom research and training program 2014\u20132018","award":["CUP B83C22002820006"],"award-info":[{"award-number":["CUP B83C22002820006"]}]},{"name":"Euratom research and training program 2014\u20132018","award":["PNRR Missione 4 Componente 2 Investimento 1.5"],"award-info":[{"award-number":["PNRR Missione 4 Componente 2 Investimento 1.5"]}]},{"name":"Sapienza University","award":["N. 755523"],"award-info":[{"award-number":["N. 755523"]}]},{"name":"Sapienza University","award":["# RM12117A805ED2FD"],"award-info":[{"award-number":["# RM12117A805ED2FD"]}]},{"name":"Sapienza University","award":["Progetto ECS 0000024 Rome Technopole"],"award-info":[{"award-number":["Progetto ECS 0000024 Rome Technopole"]}]},{"name":"Sapienza University","award":["CUP B83C22002820006"],"award-info":[{"award-number":["CUP B83C22002820006"]}]},{"name":"Sapienza University","award":["PNRR Missione 4 Componente 2 Investimento 1.5"],"award-info":[{"award-number":["PNRR Missione 4 Componente 2 Investimento 1.5"]}]},{"name":"European Union\u2014Next GenerationEU","award":["N. 755523"],"award-info":[{"award-number":["N. 755523"]}]},{"name":"European Union\u2014Next GenerationEU","award":["# RM12117A805ED2FD"],"award-info":[{"award-number":["# RM12117A805ED2FD"]}]},{"name":"European Union\u2014Next GenerationEU","award":["Progetto ECS 0000024 Rome Technopole"],"award-info":[{"award-number":["Progetto ECS 0000024 Rome Technopole"]}]},{"name":"European Union\u2014Next GenerationEU","award":["CUP B83C22002820006"],"award-info":[{"award-number":["CUP B83C22002820006"]}]},{"name":"European Union\u2014Next GenerationEU","award":["PNRR Missione 4 Componente 2 Investimento 1.5"],"award-info":[{"award-number":["PNRR Missione 4 Componente 2 Investimento 1.5"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Radiotherapy-induced cardiac toxicity and consequent diseases still represent potential severe late complications for many cancer survivors who undergo therapeutic thoracic irradiation. We aimed to assess the phenotypic and paracrine features of resident cardiac mesenchymal stromal cells (CMSCs) at early follow-up after the end of thoracic irradiation of the heart as an early sign and\/or mechanism of cardiac toxicity anticipating late organ dysfunction. Resident CMSCs were isolated from a rat model of fractionated thoracic irradiation with accurate and clinically relevant heart dosimetry that developed delayed dose-dependent cardiac dysfunction after 1 year. Cells were isolated 6 and 12 weeks after the end of radiotherapy and fully characterized at the transcriptional, paracrine, and functional levels. CMSCs displayed several altered features in a dose- and time-dependent trend, with the most impaired characteristics observed in those exposed in situ to the highest radiation dose with time. In particular, altered features included impaired cell migration and 3D growth and a and significant association of transcriptomic data with GO terms related to altered cytokine and growth factor signaling. Indeed, the altered paracrine profile of CMSCs derived from the group at the highest dose at the 12-week follow-up gave significantly reduced angiogenic support to endothelial cells and polarized macrophages toward a pro-inflammatory profile. Data collected in a clinically relevant rat model of heart irradiation simulating thoracic radiotherapy suggest that early paracrine and transcriptional alterations of the cardiac stroma may represent a dose- and time-dependent biological substrate for the delayed cardiac dysfunction phenotype observed in vivo.<\/jats:p>","DOI":"10.3390\/ijms25052873","type":"journal-article","created":{"date-parts":[[2024,3,1]],"date-time":"2024-03-01T06:07:53Z","timestamp":1709273273000},"page":"2873","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Early Impairment of Paracrine and Phenotypic Features in Resident Cardiac Mesenchymal Stromal Cells after Thoracic Radiotherapy"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1591-5118","authenticated-orcid":false,"given":"Vittorio","family":"Picchio","sequence":"first","affiliation":[{"name":"Department of Angio Cardio Neurology, IRCCS 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Medicine, Universidade de Lisboa, 1649-028 Lisbon, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4042-496X","authenticated-orcid":false,"given":"Augusto","family":"Ministro","sequence":"additional","affiliation":[{"name":"Centro Cardiovascular da Universidade de Lisboa (CCUL@RISE), Lisbon School of Medicine, Universidade de Lisboa, 1649-028 Lisbon, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0974-2206","authenticated-orcid":false,"given":"Ana Teresa","family":"Pinto","sequence":"additional","affiliation":[{"name":"Centro Cardiovascular da Universidade de Lisboa (CCUL@RISE), Lisbon School of Medicine, Universidade de Lisboa, 1649-028 Lisbon, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5220-0587","authenticated-orcid":false,"given":"Elena","family":"De 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