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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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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
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author Ninomiya, Eiichi
Hattori, Taeka
Toyoda, Masashi
Umezawa, Akihiro
Hamazaki, Takashi
Shintaku, Haruo
author_facet Ninomiya, Eiichi
Hattori, Taeka
Toyoda, Masashi
Umezawa, Akihiro
Hamazaki, Takashi
Shintaku, Haruo
author_sort Ninomiya, Eiichi
collection PubMed
description 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.
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spelling pubmed-41745472014-10-02 Glucocorticoids promote neural progenitor cell proliferation derived from human induced pluripotent stem cells Ninomiya, Eiichi Hattori, Taeka Toyoda, Masashi Umezawa, Akihiro Hamazaki, Takashi Shintaku, Haruo Springerplus Research 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. Springer International Publishing 2014-09-15 /pmc/articles/PMC4174547/ /pubmed/25279318 http://dx.doi.org/10.1186/2193-1801-3-527 Text en © Ninomiya et al.; licensee Springer. 2014 This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.
spellingShingle Research
Ninomiya, Eiichi
Hattori, Taeka
Toyoda, Masashi
Umezawa, Akihiro
Hamazaki, Takashi
Shintaku, Haruo
Glucocorticoids promote neural progenitor cell proliferation derived from human induced pluripotent stem cells
title Glucocorticoids promote neural progenitor cell proliferation derived from human induced pluripotent stem cells
title_full Glucocorticoids promote neural progenitor cell proliferation derived from human induced pluripotent stem cells
title_fullStr Glucocorticoids promote neural progenitor cell proliferation derived from human induced pluripotent stem cells
title_full_unstemmed Glucocorticoids promote neural progenitor cell proliferation derived from human induced pluripotent stem cells
title_short Glucocorticoids promote neural progenitor cell proliferation derived from human induced pluripotent stem cells
title_sort glucocorticoids promote neural progenitor cell proliferation derived from human induced pluripotent stem cells
topic Research
url 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
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