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Detection of mesenchymal stem cells senescence by prelamin A accumulation at the nuclear level

BACKGROUND: Human mesenchymal stem cells (MSC), during in vitro expansion, undergo a progressive loss of proliferative potential that leads to the senescent state, associated with a reduction of their “medicinal” properties. This may hampers their efficacy in the treatment of injured tissues. Qualit...

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Autores principales: Bellotti, Chiara, Capanni, Cristina, Lattanzi, Giovanna, Donati, Davide, Lucarelli, Enrico, Duchi, Serena
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5001959/
https://www.ncbi.nlm.nih.gov/pubmed/27625981
http://dx.doi.org/10.1186/s40064-016-3091-7
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author Bellotti, Chiara
Capanni, Cristina
Lattanzi, Giovanna
Donati, Davide
Lucarelli, Enrico
Duchi, Serena
author_facet Bellotti, Chiara
Capanni, Cristina
Lattanzi, Giovanna
Donati, Davide
Lucarelli, Enrico
Duchi, Serena
author_sort Bellotti, Chiara
collection PubMed
description BACKGROUND: Human mesenchymal stem cells (MSC), during in vitro expansion, undergo a progressive loss of proliferative potential that leads to the senescent state, associated with a reduction of their “medicinal” properties. This may hampers their efficacy in the treatment of injured tissues. Quality controls on MSC-based cell therapy products should include an assessment of the senescent state. However, a reliable and specific marker is still missing. From studies on lamin-associated disorders, has emerged the correlation between defective lamin A maturation and cellular senescence. FINDINGS: Primary cultured hMSC lines (n = 3), were analyzed by immunostaining at different life-span stages for the accumulation of prelamin A, along with other markers of cellular senescence. During culture, cells at the last stage of their life span displayed evident signs of senescence consistent with the positivity of SA-β-gal staining. We also observed a significant increase of prelamin A positive cells. Furthermore, we verified that the cells marked by prelamin A were also positive for p21(Waf1) while negative for Ki67. CONCLUSIONS: Overall data support that the detection of prelamin A identifies senescent MSC, providing an easy and reliable tool to be use alone or in combination with known senescence markers to screen MSC before their use in clinical applications. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40064-016-3091-7) contains supplementary material, which is available to authorized users.
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spelling pubmed-50019592016-09-13 Detection of mesenchymal stem cells senescence by prelamin A accumulation at the nuclear level Bellotti, Chiara Capanni, Cristina Lattanzi, Giovanna Donati, Davide Lucarelli, Enrico Duchi, Serena Springerplus Short Report BACKGROUND: Human mesenchymal stem cells (MSC), during in vitro expansion, undergo a progressive loss of proliferative potential that leads to the senescent state, associated with a reduction of their “medicinal” properties. This may hampers their efficacy in the treatment of injured tissues. Quality controls on MSC-based cell therapy products should include an assessment of the senescent state. However, a reliable and specific marker is still missing. From studies on lamin-associated disorders, has emerged the correlation between defective lamin A maturation and cellular senescence. FINDINGS: Primary cultured hMSC lines (n = 3), were analyzed by immunostaining at different life-span stages for the accumulation of prelamin A, along with other markers of cellular senescence. During culture, cells at the last stage of their life span displayed evident signs of senescence consistent with the positivity of SA-β-gal staining. We also observed a significant increase of prelamin A positive cells. Furthermore, we verified that the cells marked by prelamin A were also positive for p21(Waf1) while negative for Ki67. CONCLUSIONS: Overall data support that the detection of prelamin A identifies senescent MSC, providing an easy and reliable tool to be use alone or in combination with known senescence markers to screen MSC before their use in clinical applications. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40064-016-3091-7) contains supplementary material, which is available to authorized users. Springer International Publishing 2016-08-26 /pmc/articles/PMC5001959/ /pubmed/27625981 http://dx.doi.org/10.1186/s40064-016-3091-7 Text en © The Author(s) 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Short Report
Bellotti, Chiara
Capanni, Cristina
Lattanzi, Giovanna
Donati, Davide
Lucarelli, Enrico
Duchi, Serena
Detection of mesenchymal stem cells senescence by prelamin A accumulation at the nuclear level
title Detection of mesenchymal stem cells senescence by prelamin A accumulation at the nuclear level
title_full Detection of mesenchymal stem cells senescence by prelamin A accumulation at the nuclear level
title_fullStr Detection of mesenchymal stem cells senescence by prelamin A accumulation at the nuclear level
title_full_unstemmed Detection of mesenchymal stem cells senescence by prelamin A accumulation at the nuclear level
title_short Detection of mesenchymal stem cells senescence by prelamin A accumulation at the nuclear level
title_sort detection of mesenchymal stem cells senescence by prelamin a accumulation at the nuclear level
topic Short Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5001959/
https://www.ncbi.nlm.nih.gov/pubmed/27625981
http://dx.doi.org/10.1186/s40064-016-3091-7
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