Unraveling the aging-reversal potency of stem cell-derived extracellular vesicles in a rat model of premature cardiac senescence

Summary: Cardiosphere-derived cells (CDCs) and their extracellular vesicles (CDC-EVs) can rejuvenate and improve cardiac function, but their efficacy varies among donors. This study aimed to identify predictors of CDC-EV potency. CDCs from human donors were analyzed for phenotypical and biological p...

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Main Authors: Lidia Gómez-Cid, Alexia Campo-Fonseca, Mar Cervera-Negueruela, Alejandra Ocampo, Ángel Pinto, Juan Miguel Gil-Jaurena, Susana Suárez-Sancho, Francisco Fernández-Avilés, Lilian Grigorian-Shamagian
Format: Article
Language:English
Published: Elsevier 2025-07-01
Series:iScience
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Online Access:http://www.sciencedirect.com/science/article/pii/S258900422501171X
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author Lidia Gómez-Cid
Alexia Campo-Fonseca
Mar Cervera-Negueruela
Alejandra Ocampo
Ángel Pinto
Juan Miguel Gil-Jaurena
Susana Suárez-Sancho
Francisco Fernández-Avilés
Lilian Grigorian-Shamagian
author_facet Lidia Gómez-Cid
Alexia Campo-Fonseca
Mar Cervera-Negueruela
Alejandra Ocampo
Ángel Pinto
Juan Miguel Gil-Jaurena
Susana Suárez-Sancho
Francisco Fernández-Avilés
Lilian Grigorian-Shamagian
author_sort Lidia Gómez-Cid
collection DOAJ
description Summary: Cardiosphere-derived cells (CDCs) and their extracellular vesicles (CDC-EVs) can rejuvenate and improve cardiac function, but their efficacy varies among donors. This study aimed to identify predictors of CDC-EV potency. CDCs from human donors were analyzed for phenotypical and biological properties. The anti-aging activity of CDC-EVs was tested using an in vitro matrix assay. Results showed that donor age did not determine potency, but CDC senescence correlated with most bioactive properties. However, senescence alone was insufficient to predict CDC-EV potency. CDC-EVs were classified as more potent (P-EVs) or less potent (NP-EVs) based on assay performance. In a rat model of premature cardiac aging, P-EVs reduced senescence-associated GLB1 gene expression and protected against hypertrophy and fibrosis, while NP-EVs had negative effects. The study concludes that CDC-EV anti-aging potency cannot be predicted by donor age or CDC senescence, proposing an in vitro potency assay for evaluating CDC-EVs before clinical use.
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spelling doaj-art-e97b8548897d4c85a7341b0de7ccb3922025-08-20T03:30:19ZengElsevieriScience2589-00422025-07-0128711291010.1016/j.isci.2025.112910Unraveling the aging-reversal potency of stem cell-derived extracellular vesicles in a rat model of premature cardiac senescenceLidia Gómez-Cid0Alexia Campo-Fonseca1Mar Cervera-Negueruela2Alejandra Ocampo3Ángel Pinto4Juan Miguel Gil-Jaurena5Susana Suárez-Sancho6Francisco Fernández-Avilés7Lilian Grigorian-Shamagian8Departamento de Bioingeniería, IiSGM, Universidad Carlos III de Madrid, 28911 Leganés, SpainDepartamento de Bioingeniería, IiSGM, Universidad Carlos III de Madrid, 28911 Leganés, SpainDepartamento de Bioingeniería, IiSGM, Universidad Carlos III de Madrid, 28911 Leganés, SpainUnidad de Producción Celular, Hospital General Universitario Gregorio Marañón, 28009 Madrid, SpainHospital General Universitario Gregorio Marañón, 28009 Madrid, SpainHospital General Universitario Gregorio Marañón, 28009 Madrid, SpainUnidad de Producción Celular, Hospital General Universitario Gregorio Marañón, 28009 Madrid, SpainFaculty of Medicine, Universidad Complutense de Madrid, 28040 Madrid, Spain; Cardiology Department, San Rafael University Hospital, Universidad Francisco de Vitoria, Madrid, SpainCardiology Department, San Rafael University Hospital, Universidad Francisco de Vitoria, Madrid, Spain; Corresponding authorSummary: Cardiosphere-derived cells (CDCs) and their extracellular vesicles (CDC-EVs) can rejuvenate and improve cardiac function, but their efficacy varies among donors. This study aimed to identify predictors of CDC-EV potency. CDCs from human donors were analyzed for phenotypical and biological properties. The anti-aging activity of CDC-EVs was tested using an in vitro matrix assay. Results showed that donor age did not determine potency, but CDC senescence correlated with most bioactive properties. However, senescence alone was insufficient to predict CDC-EV potency. CDC-EVs were classified as more potent (P-EVs) or less potent (NP-EVs) based on assay performance. In a rat model of premature cardiac aging, P-EVs reduced senescence-associated GLB1 gene expression and protected against hypertrophy and fibrosis, while NP-EVs had negative effects. The study concludes that CDC-EV anti-aging potency cannot be predicted by donor age or CDC senescence, proposing an in vitro potency assay for evaluating CDC-EVs before clinical use.http://www.sciencedirect.com/science/article/pii/S258900422501171XBiological sciencesCell biologyBiological sciences research methodologies
spellingShingle Lidia Gómez-Cid
Alexia Campo-Fonseca
Mar Cervera-Negueruela
Alejandra Ocampo
Ángel Pinto
Juan Miguel Gil-Jaurena
Susana Suárez-Sancho
Francisco Fernández-Avilés
Lilian Grigorian-Shamagian
Unraveling the aging-reversal potency of stem cell-derived extracellular vesicles in a rat model of premature cardiac senescence
iScience
Biological sciences
Cell biology
Biological sciences research methodologies
title Unraveling the aging-reversal potency of stem cell-derived extracellular vesicles in a rat model of premature cardiac senescence
title_full Unraveling the aging-reversal potency of stem cell-derived extracellular vesicles in a rat model of premature cardiac senescence
title_fullStr Unraveling the aging-reversal potency of stem cell-derived extracellular vesicles in a rat model of premature cardiac senescence
title_full_unstemmed Unraveling the aging-reversal potency of stem cell-derived extracellular vesicles in a rat model of premature cardiac senescence
title_short Unraveling the aging-reversal potency of stem cell-derived extracellular vesicles in a rat model of premature cardiac senescence
title_sort unraveling the aging reversal potency of stem cell derived extracellular vesicles in a rat model of premature cardiac senescence
topic Biological sciences
Cell biology
Biological sciences research methodologies
url http://www.sciencedirect.com/science/article/pii/S258900422501171X
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