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Early impairment of paracrine and phenotypic features in resident cardiac mesenchymal stromal cells after thoracic radiotherapy

2024Journal article Open access
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dc.contributor.authorPicchio, Vittorio
dc.contributor.authorGaetani, Roberto
dc.contributor.authorPagano, Francesca
dc.contributor.authorDerevyanchuk, Yuriy
dc.contributor.authorPagliarosi, Olivia
dc.contributor.authorFloris, Erica
dc.contributor.authorCozzolino, Claudia
dc.contributor.authorBernava, Giacomo
dc.contributor.authorBordin, Antonella
dc.contributor.authorRocha, Filipe
dc.contributor.authorPereira, Ana
dc.contributor.authorMinistro, Augusto
dc.contributor.authorPinto, Ana
dc.contributor.authorDe Falco, Elena
dc.contributor.authorSerino, Gianpaolo
dc.contributor.authorMassai, Diana
dc.contributor.authorTamarat, Radia
dc.contributor.authorPesce, Maurizio
dc.contributor.authorSantos, Susana Constantino Rosa
dc.contributor.authorMessina, Elisa
dc.contributor.authorChimenti, Isotta
dc.date.accessioned2024-03-22T15:03:50Z
dc.date.available2024-03-22T15:03:50Z
dc.date.issued2024
dc.description© 2024 by the authors. 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/).pt_PT
dc.description.abstractRadiotherapy-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.pt_PT
dc.description.sponsorshipThis work was supported by the MEDIRAD project, which received funding from the Euratom research and training program 2014–2018 under grant agreement N. 755523. This work was also supported by grant # RM12117A805ED2FD from Sapienza University to IC. EDF is supported by grant “Progetto ECS 0000024 Rome Technopole, CUP B83C22002820006, PNRR Missione 4 Componente 2 Investimento 1.5”, funded by the European Union—Next GenerationEU.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationInt J Mol Sci. 2024 Mar 1;25(5):2873pt_PT
dc.identifier.doi10.3390/ijms25052873pt_PT
dc.identifier.eissn1422-0067
dc.identifier.issn1661-6596
dc.identifier.urihttp://hdl.handle.net/10451/63701
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherMDPIpt_PT
dc.relationImplications of Medical Low Dose Radiation Exposure
dc.relation.publisherversionhttps://www.mdpi.com/journal/ijmspt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectCardiac fibrosispt_PT
dc.subjectCardiac stromal cellspt_PT
dc.subjectCardiotoxicitypt_PT
dc.subjectRadiation-induced cardiomyopathypt_PT
dc.subjectRadiation-induced heart diseasept_PT
dc.subjectRadiotherapypt_PT
dc.titleEarly impairment of paracrine and phenotypic features in resident cardiac mesenchymal stromal cells after thoracic radiotherapypt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleImplications of Medical Low Dose Radiation Exposure
oaire.awardURIinfo:eu-repo/grantAgreement/EC/H2020/755523/EU
oaire.citation.issue5pt_PT
oaire.citation.titleInternational Journal of Molecular Sciencespt_PT
oaire.citation.volume25pt_PT
oaire.fundingStreamH2020
person.familyNameNunes Rocha
person.familyNamePereira
person.familyNameAlmeida Ministro
person.familyNamePinto
person.familyNameConstantino Rosa Santos
person.givenNameFilipe
person.givenNameAna
person.givenNameAugusto Manuel
person.givenNameAna
person.givenNameSusana
person.identifier1814324
person.identifier.ciencia-id9116-62E0-C95F
person.identifier.ciencia-id1F12-4544-1A00
person.identifier.ciencia-idF11D-8C75-78BF
person.identifier.orcid0000-0002-0095-0052
person.identifier.orcid0000-0002-9057-0781
person.identifier.orcid0000-0003-4042-496X
person.identifier.orcid0000-0003-0974-2206
person.identifier.orcid0000-0002-5711-1292
project.funder.identifierhttp://doi.org/10.13039/501100008530
project.funder.nameEuropean Commission
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublicationff5a3d26-0dbb-4fc7-ac39-c6dbeb4636fa
relation.isAuthorOfPublication91fd8d9a-e339-4481-8f23-19fbcaa11c97
relation.isAuthorOfPublication6cd64629-69ea-4cf3-bb87-919df93d3df8
relation.isAuthorOfPublication7dea5918-dffc-457e-a03b-7aead3d12745
relation.isAuthorOfPublicationbbd5fe87-d7bb-431a-8f61-37e86fd4d2f6
relation.isAuthorOfPublication.latestForDiscovery7dea5918-dffc-457e-a03b-7aead3d12745
relation.isProjectOfPublication6e355f44-32a5-4673-9966-9bae53976d5f
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