2026-06-14T02:29:48Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/74762024-11-29T15:39:01Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
Kannappan, Ramaswamy
author
Matsuda, Alex
author
Ferreira-Martins, João
author
Zhang, Eric
author
Palano, Giorgia
author
Czarna, Anna
author
Cabral-Da-Silva, Mauricio Castro
author
Bastos-Carvalho, Adriana
author
Sanada, Fumihiro
author
Ide, Noriko
author
Rota, Marcello
author
Blasco , MA
author
Serrano Marugan, Manuel
author
Anversa, Piero
author
Leri, Annarosa
funder
National Institutes of Health (Estados Unidos)
funder
Cardiocentro Ticino Foundation
2019-04-22T11:39:04Z
2019-04-22T11:39:04Z
2017-01-31
EBioMedicine. 2017;16:224-237.
10.1016/j.ebiom.2017.01.028
2352-3964
23523964
EBioMedicine
28163043
http://hdl.handle.net/20.500.12105/7476
p53 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.
eng
DNA repair
Diabetes
Stem cell engraftment
Stem cell fate
p53 Modulates the Fate of Cardiac Progenitor Cells Ex Vivo and in the Diabetic Heart In Vivo
journal article
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p53ModulatestheFateof_2017.pdf
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https://repisalud.isciii.es/bitstreams/22c0ff69-2819-43a8-9051-58dbdc48bde2/download
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p53ModulatestheFateof_2017.pdf.txt