A cell engineering strategy to enhance the safety of stem cell therapies.
Cell Rep
; 8(6): 1677-1685, 2014 Sep 25.
Article
en En
| MEDLINE
| ID: mdl-25242333
ABSTRACT
The long-term risk of malignancy associated with stem cell therapies is a significant concern in the clinical application of this exciting technology. We report a cancer-selective strategy to enhance the safety of stem cell therapies. Briefly, using a cell engineering approach, we show that aggressive cancers derived from human or murine induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs) are strikingly sensitive to temporary MYC blockade. On the other hand, differentiated tissues derived from human or mouse iPSCs can readily tolerate temporary MYC inactivation. In cancer cells, endogenous MYC is required to maintain the metabolic and epigenetic functions of the embryonic and cancer-specific pyruvate kinase M2 isoform (PKM2). In summary, our results implicate PKM2 in cancer's increased MYC dependence and indicate dominant MYC inhibition as a cancer-selective fail-safe for stem cell therapies.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Células Madre Pluripotentes Inducidas
/
Ingeniería Celular
/
Tratamiento Basado en Trasplante de Células y Tejidos
Tipo de estudio:
Diagnostic_studies
Límite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
Cell Rep
Año:
2014
Tipo del documento:
Article
País de afiliación:
Estados Unidos