The telomerase inhibitor AZT enhances differentiation and prevents overgrowth of human pluripotent stem cell-derived neural progenitors.
J Biol Chem
; 293(23): 8722-8733, 2018 06 08.
Article
en En
| MEDLINE
| ID: mdl-29628445
ABSTRACT
Human pluripotent stem cell (hPSC)-based cell-replacement therapy has emerged as a promising approach for addressing numerous neurological diseases. However, hPSC transplantation has the potential to cause human cell overgrowth and cancer, which represents a major obstacle to implementing hPSC-based therapies. Inhibition of the overgrowth of transplanted cells could help reduce the risk for hPSC transplantation-induced tumorigenesis. In this study, we report that the telomerase inhibitor azidothymidine (3'-azido-3'-deoxythymidine; AZT) enhances the differentiation of cortical neurons and significantly suppresses the proliferation of hPSC-derived cortical progenitors. Using human embryonic stem cells and induced pluripotent stem cells in culture, we found that AZT effectively reduces the number of dividing progenitors without inducing cell death. Furthermore, AZT promoted differentiation of cortical progenitors and maturation of cortical neurons. Of note, AZT-pretreated, hPSC-derived neural progenitors exhibited decreased proliferation and increased differentiation into cortical neurons when transplanted into the mouse brain. In summary, our findings indicate that AZT prevents the overgrowth of hPSC-derived neural precursors and enhances the differentiation of cortical neurons in both cell cultures and hPSC-transplanted mouse brain. We propose that our work could inform clinical applications of hPSC-based cell therapy.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Zidovudina
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Telomerasa
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Técnicas de Cultivo de Célula
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Células Madre Pluripotentes
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Inhibidores Enzimáticos
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Células-Madre Neurales
Límite:
Animals
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Humans
Idioma:
En
Revista:
J Biol Chem
Año:
2018
Tipo del documento:
Article