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Glucocorticoids promote neural progenitor cell proliferation derived from human induced pluripotent stem cells

Glucocorticoids (GCs) are frequently used for treating and preventing chronic lung disease and circulatory dysfunction in premature infants. However, there is growing concern about the detrimental effects of systemic GC administration on neurodevelopment. The first choice of GCs to minimize the adve...

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Detalles Bibliográficos
Autores principales: Ninomiya, Eiichi, Hattori, Taeka, Toyoda, Masashi, Umezawa, Akihiro, Hamazaki, Takashi, Shintaku, Haruo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4174547/
https://www.ncbi.nlm.nih.gov/pubmed/25279318
http://dx.doi.org/10.1186/2193-1801-3-527
Descripción
Sumario:Glucocorticoids (GCs) are frequently used for treating and preventing chronic lung disease and circulatory dysfunction in premature infants. However, there is growing concern about the detrimental effects of systemic GC administration on neurodevelopment. The first choice of GCs to minimize the adverse effects on the developing brain is still under debate. We investigated the effect of commonly used GCs such as dexamethasone (DEX), betamethasone (BET) and hydrocortisone (HDC) on the proliferation of human-induced pluripotent stem cell (iPSC)-derived neuronal progenitor cells (NPCs). In this study, NPCs were treated with various concentrations of GCs and subjected to cell proliferation assays. Furthermore, we quantified the number of microtubule-associated protein 2 (MAP2) positive neurons in NPCs by immunostaining. All GCs promoted NPC proliferation in a dose-dependent manner. We also confirmed that MAP2-positive neurons in NPCs increased upon GC treatment. However, differential effects of GCs on MAP2 positive neurons were observed when we treated NPCs with H(2)O(2). The total numbers of NPCs increased upon any GC treatment even under oxidative conditions but the numbers of MAP2 positive neurons increased only by HDC treatment. GCs promoted human iPSCs–derived NPC proliferation and the differential effects of GCs became apparent under oxidative stress. Our results may support HDC as the preferred choice over DEX and BET to prevent adverse effects on the developing human brain. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/2193-1801-3-527) contains supplementary material, which is available to authorized users.