Increased dosage of tumor suppressors limits the tumorigenicity of iPS cells without affecting their pluripotency

Embryonic stem (ES) cells and induced pluripotent stem (iPS) cells represent a promising therapeutic tool for many diseases, including aged tissues and organs at high risk of failure. However, the intrinsic self-renewal and pluripotency of ES and iPS cells make them tumorigenic, and hence, the risk...

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Autores: Menendez, Sergio, Camus, Suzanne, Herreria, Aida, Paramonov, Ida, Morera, Laura B., Collado, Manuel, Pekarik, Vlad, Maceda, Iago, Edel, Michael John, Consiglio, Antonella, Sánchez-Danés, Adriana, Li, Han, Serrano Marugán, Manuel, Izpisúa Belmonte, Juan Carlos
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2012
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/107066
Acceso en línea:https://hdl.handle.net/2445/107066
Access Level:acceso abierto
Palabra clave:Cèl·lules mare embrionàries
Proteïnes supressores de tumors
Càncer
Transformació cel·lular
Envelliment
Embryonic stem cells
Tumor suppressor protein
Cancer
Cell transformation
Aging
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spelling Increased dosage of tumor suppressors limits the tumorigenicity of iPS cells without affecting their pluripotencyMenendez, SergioCamus, SuzanneHerreria, AidaParamonov, IdaMorera, Laura B.Collado, ManuelPekarik, VladMaceda, IagoEdel, Michael JohnConsiglio, AntonellaSánchez-Danés, AdrianaLi, HanSerrano Marugán, ManuelIzpisúa Belmonte, Juan CarlosCèl·lules mare embrionàriesProteïnes supressores de tumorsCàncerTransformació cel·lularEnvellimentEmbryonic stem cellsTumor suppressor proteinCancerCell transformationAgingEmbryonic stem (ES) cells and induced pluripotent stem (iPS) cells represent a promising therapeutic tool for many diseases, including aged tissues and organs at high risk of failure. However, the intrinsic self-renewal and pluripotency of ES and iPS cells make them tumorigenic, and hence, the risk of tumor development hinders their clinical application. Here, we present a novel approach to limit their tumorigenicity and increase their safety through increased copy number of tumor suppressors. iPS containing an extra copy of the p53 or Ink4a/ARF locus show normal pluripotency, as determined by in vitro and in vivo differentiation assays. Yet, while retaining full pluripotency, they also possess an improved engagement of the p53 pathway during teratocarcinoma formation, which leads to a reduced tumorigenic potential in various in vitro and in vivo assays. Furthermore, they show an improved response to anticancer drugs, which could aid in their elimination in case tumors arise with no adverse effects on cell function or aging. Our system provides a model for studying tumor suppressor pathways during reprogramming, differentiation, and cell therapy applications. This offers an improved understanding of the pathways involved in tumor growth from engrafted pluripotent stem cells, which could facilitate the use of ES and iPS cells in regenerative medicine.John Wiley & Sons2017201720122017info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion10 p.application/pdfhttps://hdl.handle.net/2445/107066Articles publicats en revistes (Patologia i Terapèutica Experimental)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1111/j.1474-9726.2011.00754.xAging Cell, 2012, vol. 11, num. 1, p. 41-50https://doi.org/10.1111/j.1474-9726.2011.00754.x(c) Menendez, Sergio et al., 2012info:eu-repo/semantics/openAccessoai:recercat.cat:2445/1070662026-05-29T05:05:01Z
dc.title.none.fl_str_mv Increased dosage of tumor suppressors limits the tumorigenicity of iPS cells without affecting their pluripotency
title Increased dosage of tumor suppressors limits the tumorigenicity of iPS cells without affecting their pluripotency
spellingShingle Increased dosage of tumor suppressors limits the tumorigenicity of iPS cells without affecting their pluripotency
Menendez, Sergio
Cèl·lules mare embrionàries
Proteïnes supressores de tumors
Càncer
Transformació cel·lular
Envelliment
Embryonic stem cells
Tumor suppressor protein
Cancer
Cell transformation
Aging
title_short Increased dosage of tumor suppressors limits the tumorigenicity of iPS cells without affecting their pluripotency
title_full Increased dosage of tumor suppressors limits the tumorigenicity of iPS cells without affecting their pluripotency
title_fullStr Increased dosage of tumor suppressors limits the tumorigenicity of iPS cells without affecting their pluripotency
title_full_unstemmed Increased dosage of tumor suppressors limits the tumorigenicity of iPS cells without affecting their pluripotency
title_sort Increased dosage of tumor suppressors limits the tumorigenicity of iPS cells without affecting their pluripotency
dc.creator.none.fl_str_mv Menendez, Sergio
Camus, Suzanne
Herreria, Aida
Paramonov, Ida
Morera, Laura B.
Collado, Manuel
Pekarik, Vlad
Maceda, Iago
Edel, Michael John
Consiglio, Antonella
Sánchez-Danés, Adriana
Li, Han
Serrano Marugán, Manuel
Izpisúa Belmonte, Juan Carlos
author Menendez, Sergio
author_facet Menendez, Sergio
Camus, Suzanne
Herreria, Aida
Paramonov, Ida
Morera, Laura B.
Collado, Manuel
Pekarik, Vlad
Maceda, Iago
Edel, Michael John
Consiglio, Antonella
Sánchez-Danés, Adriana
Li, Han
Serrano Marugán, Manuel
Izpisúa Belmonte, Juan Carlos
author_role author
author2 Camus, Suzanne
Herreria, Aida
Paramonov, Ida
Morera, Laura B.
Collado, Manuel
Pekarik, Vlad
Maceda, Iago
Edel, Michael John
Consiglio, Antonella
Sánchez-Danés, Adriana
Li, Han
Serrano Marugán, Manuel
Izpisúa Belmonte, Juan Carlos
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Cèl·lules mare embrionàries
Proteïnes supressores de tumors
Càncer
Transformació cel·lular
Envelliment
Embryonic stem cells
Tumor suppressor protein
Cancer
Cell transformation
Aging
topic Cèl·lules mare embrionàries
Proteïnes supressores de tumors
Càncer
Transformació cel·lular
Envelliment
Embryonic stem cells
Tumor suppressor protein
Cancer
Cell transformation
Aging
description Embryonic stem (ES) cells and induced pluripotent stem (iPS) cells represent a promising therapeutic tool for many diseases, including aged tissues and organs at high risk of failure. However, the intrinsic self-renewal and pluripotency of ES and iPS cells make them tumorigenic, and hence, the risk of tumor development hinders their clinical application. Here, we present a novel approach to limit their tumorigenicity and increase their safety through increased copy number of tumor suppressors. iPS containing an extra copy of the p53 or Ink4a/ARF locus show normal pluripotency, as determined by in vitro and in vivo differentiation assays. Yet, while retaining full pluripotency, they also possess an improved engagement of the p53 pathway during teratocarcinoma formation, which leads to a reduced tumorigenic potential in various in vitro and in vivo assays. Furthermore, they show an improved response to anticancer drugs, which could aid in their elimination in case tumors arise with no adverse effects on cell function or aging. Our system provides a model for studying tumor suppressor pathways during reprogramming, differentiation, and cell therapy applications. This offers an improved understanding of the pathways involved in tumor growth from engrafted pluripotent stem cells, which could facilitate the use of ES and iPS cells in regenerative medicine.
publishDate 2012
dc.date.none.fl_str_mv 2012
2017
2017
2017
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/107066
url https://hdl.handle.net/2445/107066
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1111/j.1474-9726.2011.00754.x
Aging Cell, 2012, vol. 11, num. 1, p. 41-50
https://doi.org/10.1111/j.1474-9726.2011.00754.x
dc.rights.none.fl_str_mv (c) Menendez, Sergio et al., 2012
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) Menendez, Sergio et al., 2012
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 10 p.
application/pdf
dc.publisher.none.fl_str_mv John Wiley & Sons
publisher.none.fl_str_mv John Wiley & Sons
dc.source.none.fl_str_mv Articles publicats en revistes (Patologia i Terapèutica Experimental)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869408199981924352
score 15,81155

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