Isolation of human induced pluripotent stem cell-derived dopaminergic progenitors by cell sorting for successful transplantation.
Stem Cell Reports
; 2(3): 337-50, 2014 Mar 11.
Article
en En
| MEDLINE
| ID: mdl-24672756
ABSTRACT
Human induced pluripotent stem cells (iPSCs) can provide a promising source of midbrain dopaminergic (DA) neurons for cell replacement therapy for Parkinson's disease. However, iPSC-derived donor cells inevitably contain tumorigenic or inappropriate cells. Here, we show that human iPSC-derived DA progenitor cells can be efficiently isolated by cell sorting using a floor plate marker, CORIN. We induced DA neurons using scalable culture conditions on human laminin fragment, and the sorted CORIN(+) cells expressed the midbrain DA progenitor markers, FOXA2 and LMX1A. When transplanted into 6-OHDA-lesioned rats, the CORIN(+) cells survived and differentiated into midbrain DA neurons in vivo, resulting in significant improvement of the motor behavior, without tumor formation. In particular, the CORIN(+) cells in a NURR1(+) cell-dominant stage exhibited the best survival and function as DA neurons. Our method is a favorable strategy in terms of scalability, safety, and efficiency and may be advantageous for clinical application.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Diferenciación Celular
/
Células Madre Pluripotentes Inducidas
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Neuronas Dopaminérgicas
Límite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Stem Cell Reports
Año:
2014
Tipo del documento:
Article
País de afiliación:
Japón