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dc.contributor.authorKannappan, Ramaswamy
dc.contributor.authorMatsuda, Alex
dc.contributor.authorFerreira-Martins, João
dc.contributor.authorZhang, Eric
dc.contributor.authorPalano, Giorgia
dc.contributor.authorCzarna, Anna
dc.contributor.authorCabral-Da-Silva, Mauricio Castro
dc.contributor.authorBastos-Carvalho, Adriana
dc.contributor.authorSanada, Fumihiro
dc.contributor.authorIde, Noriko
dc.contributor.authorRota, Marcello
dc.contributor.authorBlasco , MA 
dc.contributor.authorSerrano Marugan, Manuel 
dc.contributor.authorAnversa, Piero
dc.contributor.authorLeri, Annarosa
dc.identifier.citationEBioMedicine. 2017;16:224-237.es_ES
dc.description.abstractp53 is an important modulator of stem cell fate, but its role in cardiac progenitor cells (CPCs) is unknown. Here, we tested the effects of a single extra-copy of p53 on the function of CPCs in the presence of oxidative stress mediated by doxorubicin in vitro and type-1 diabetes in vivo. CPCs were obtained from super-p53 transgenic mice (p53-tg), in which the additional allele is regulated in a manner similar to the endogenous protein. Old CPCs with increased p53 dosage showed a superior ability to sustain oxidative stress, repair DNA damage and restore cell division. With doxorubicin, a larger fraction of CPCs carrying an extra-copy of the p53 allele recruited γH2A.X reestablishing DNA integrity. Enhanced p53 expression resulted in a superior tolerance to oxidative stress in vivo by providing CPCs with defense mechanisms necessary to survive in the milieu of the diabetic heart; they engrafted in regions of tissue injury and in three days acquired the cardiomyocyte phenotype. The biological advantage provided by the increased dosage of p53 in CPCs suggests that this genetic strategy may be translated to humans to increase cellular engraftment and growth, critical determinants of successful cell therapy for the failing heart.es_ES
dc.relation.isversionofPublisher's versiones_ES
dc.subjectDNA repaires_ES
dc.subjectStem cell engraftmentes_ES
dc.subjectStem cell fatees_ES
dc.subject.meshAnimals es_ES
dc.subject.meshBlotting, Westernes_ES
dc.subject.meshCell Differentiation es_ES
dc.subject.meshCell Proliferation es_ES
dc.subject.meshCells, Cultured es_ES
dc.subject.meshDiabetes Mellitus, Experimental es_ES
dc.subject.meshDiabetes Mellitus, Type 1 es_ES
dc.subject.meshFemale es_ES
dc.subject.meshGene Expression es_ES
dc.subject.meshHeart es_ES
dc.subject.meshHistones es_ES
dc.subject.meshHumans es_ES
dc.subject.meshMale es_ES
dc.subject.meshMice, Inbred C57BL es_ES
dc.subject.meshMice, Transgenic es_ES
dc.subject.meshMicroscopy, Fluorescence es_ES
dc.subject.meshMyocardium es_ES
dc.subject.meshMyocytes, Cardiaces_ES
dc.subject.meshReverse Transcriptase Polymerase Chain Reaction es_ES
dc.subject.meshStem Cell Transplantation es_ES
dc.subject.meshStem Cells es_ES
dc.subject.meshTumor Suppressor Protein p53 es_ES
dc.titlep53 Modulates the Fate of Cardiac Progenitor Cells Ex Vivo and in the Diabetic Heart In Vivoes_ES
dc.rights.licenseAtribución-NoComercial 4.0 Internacional*
dc.contributor.funderNational Institutes of Health (United States)es_ES
dc.contributor.funderCardiocentro Ticino Foundationes_ES
dc.repisalud.orgCNIOCNIO::Grupos de investigación::Grupo de Telómeros y Telomerasaes_ES

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