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@article{1085356,
author = {Menendez, Sergio and Camus, Suzanne and Herreria, Aida and Paramonov, Ida and Morera, Laura B and Collado, Manuel and Pekařík, Vladimír and Maceda, Iago and Edel, Michael and Consiglio, Antonella and Sanchez, Adriana and Li, Han and Serrano, Manuel and Belmonte, Juan C I},
article_location = {MALDEN, USA},
article_number = {1},
doi = {http://dx.doi.org/10.1111/j.1474-9726.2011.00754.x},
keywords = {induced pluripotent stem; embryonic stem; tumorigenicity; p53; Ink4a; ARF; reprogramming},
language = {eng},
issn = {1474-9718},
journal = {AGING CELL},
title = {Increased dosage of tumor suppressors limits the tumorigenicity of iPS cells without affecting their pluripotency},
volume = {11},
year = {2012}
}
TY - JOUR
ID - 1085356
AU - Menendez, Sergio - Camus, Suzanne - Herreria, Aida - Paramonov, Ida - Morera, Laura B - Collado, Manuel - Pekařík, Vladimír - Maceda, Iago - Edel, Michael - Consiglio, Antonella - Sanchez, Adriana - Li, Han - Serrano, Manuel - Belmonte, Juan C I
PY - 2012
TI - Increased dosage of tumor suppressors limits the tumorigenicity of iPS cells without affecting their pluripotency
JF - AGING CELL
VL - 11
IS - 1
SP - 41-50
EP - 41-50
PB - WILEY-BLACKWELL
SN - 14749718
KW - induced pluripotent stem
KW - embryonic stem
KW - tumorigenicity
KW - p53
KW - Ink4a
KW - ARF
KW - reprogramming
N2 - 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.
ER -
MENENDEZ, Sergio, Suzanne CAMUS, Aida HERRERIA, Ida PARAMONOV, Laura B MORERA, Manuel COLLADO, Vladimír PEKAŘÍK, Iago MACEDA, Michael EDEL, Antonella CONSIGLIO, Adriana SANCHEZ, Han LI, Manuel SERRANO a Juan C I BELMONTE. Increased dosage of tumor suppressors limits the tumorigenicity of iPS cells without affecting their pluripotency. \textit{AGING CELL}. MALDEN, USA: WILEY-BLACKWELL, 2012, roč.~11, č.~1, s.~41-50. ISSN~1474-9718. Dostupné z: https://dx.doi.org/10.1111/j.1474-9726.2011.00754.x.
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