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Title: Increased dosage of tumor suppressors limits the tumorigenicity of iPS cells without affecting their pluripotency
Author: 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, Manuel
Izpisúa Belmonte, Juan Carlos
Keywords: Cèl·lules mare embrionàries
Proteïnes supressores de tumors
Transformació cel·lular
Embryonic stem cells
Tumor suppressor protein
Cell transformation
Issue Date: 12-Jan-2012
Publisher: John Wiley & Sons
Abstract: 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.
Note: Reproducció del document publicat a:
It is part of: Aging Cell, 2012, vol. 11, num. 1, p. 41-50
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ISSN: 1474-9718
Appears in Collections:Articles publicats en revistes (Institut de Biomedicina (IBUB))
Articles publicats en revistes (Patologia i Terapèutica Experimental)

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