Teratogenic potential in cultures optimized for oligodendrocyte development from mouse embryonic stem cells.
Stem Cells Dev
; 19(9): 1343-53, 2010 Sep.
Article
em En
| MEDLINE
| ID: mdl-20131970
ABSTRACT
We describe a rapid and efficient 5-step program of defined factors for the genesis of brain myelin-forming oligodendrocytes (OLs) from embryonic stem cells (ESCs). The OLs emerge on the same time frame in vitro as seen in vivo. Factors promoting neural induction (retinoids, noggin) are required, while exogenous Sonic hedgehog is not. In contrast we were unable to generate OLs by trans-differentiation of ethically neutral mesenchymal stem cells, indicating a requirement for cis-differentiation via neural ectoderm for OL genesis. In the ESC-derived cultures, our optimized protocol generated a mixed population with 49% O4(+), Olig2(+) OL lineage cells. These cultures also retained pluripotential markers including Oct4, and an analysis of embryoid body formation in vitro, and allogeneic grafts in vivo, revealed that the ESC-derived cultures also retained teratogenic cells. The frequency of embryoid body formation from terminal differentiated OL cultures was 0.001%, 100-fold lower than that from ESCs. Our results provide the first quantitative measurement of teratogenicity in ESC-derived, exhaustively differentiated allogeneic grafts, and demonstrate the unequivocal need to purify ESC-derived cells in order to generate a safe population for regenerative therapy.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Teratogênicos
/
Diferenciação Celular
/
Oligodendroglia
/
Células-Tronco Embrionárias
Tipo de estudo:
Evaluation_studies
/
Guideline
/
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Stem Cells Dev
Assunto da revista:
HEMATOLOGIA
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Estados Unidos