TY - JOUR
T1 - Resilience to transformation and inherent genetic and functional stability of adult neural stem cells ex vivo
AU - Foroni, Chiara
AU - Galli, Rossella
AU - Cipelletti, Barbara
AU - Caumo, Andrea
AU - Alberti, Sara
AU - Fiocco, Roberta
AU - Vescovi, Angelo
N1 - Copyright:
Copyright 2011 Elsevier B.V., All rights reserved.
PY - 2007/4/15
Y1 - 2007/4/15
N2 - Recent observations have suggested that extensive culturing of adult neural stem cells (ANSCs) by exploiting the NeuroSphere assay might select for aggressive cell clones, endowed with neoplastic potential, that overgrow the rest of the native stem cells. However, a detailed study of the propensity of ANSCs to transform has never been thoroughly undertaken. Here, we report the first demonstration that ANSCs can be propagated in vitro for over a year, maintaining a strikingly stable profile with regard to self-renewal, differentiation, growth factor dependence, karyotype, and molecular profiling. Most importantly, the long-term culturing of ANSCs did not result in the formation of tumors in vivo, even when ANSCs were transduced with Myc and Ras oncogenes. The cancer resistance could depend on specific mechanisms aimed at protecting ANSCs and preserved by optimal nonstressful culture conditions. In conclusion, besides a plentiful and safe source of cells for therapeutic applications, ANSCs provide an ideal model to study aging and cancer in the context of stemness.
AB - Recent observations have suggested that extensive culturing of adult neural stem cells (ANSCs) by exploiting the NeuroSphere assay might select for aggressive cell clones, endowed with neoplastic potential, that overgrow the rest of the native stem cells. However, a detailed study of the propensity of ANSCs to transform has never been thoroughly undertaken. Here, we report the first demonstration that ANSCs can be propagated in vitro for over a year, maintaining a strikingly stable profile with regard to self-renewal, differentiation, growth factor dependence, karyotype, and molecular profiling. Most importantly, the long-term culturing of ANSCs did not result in the formation of tumors in vivo, even when ANSCs were transduced with Myc and Ras oncogenes. The cancer resistance could depend on specific mechanisms aimed at protecting ANSCs and preserved by optimal nonstressful culture conditions. In conclusion, besides a plentiful and safe source of cells for therapeutic applications, ANSCs provide an ideal model to study aging and cancer in the context of stemness.
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U2 - 10.1158/0008-5472.CAN-06-4577
DO - 10.1158/0008-5472.CAN-06-4577
M3 - Article
C2 - 17440085
AN - SCOPUS:34248595985
SN - 0008-5472
VL - 67
SP - 3725
EP - 3733
JO - Cancer research
JF - Cancer research
IS - 8
ER -