title: Glucocorticoids promote neural progenitor cell proliferation derived from human induced pluripotent stem cells.
abstract: 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 H2O2. 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 iPSCsâ€"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.
authors.affiliation: Department of Pediatrics, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585 Japan.
authors.forename: Eiichi
authors.initials: E
authors.lastname: Ninomiya
authors.affiliation: Department of Pediatrics, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585 Japan.
authors.forename: Taeka
authors.initials: T
authors.lastname: Hattori
authors.affiliation: Research Team for Geriatric Medicine (Vascular Medicine), Tokyo Metropolitan Institute of Gerontology, Sakaecho 35-2, Itabashi-Ku, Tokyo, 173-0015 Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Toyoda
authors.affiliation: Department of Reproductive Biology, National Research Institute for Child Health and Development, 2-10-1 Ookura, Setagaya-ku, Tokyo, 157-8535 Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Umezawa
authors.affiliation: Department of Pediatrics, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585 Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Hamazaki
authors.affiliation: Department of Pediatrics, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585 Japan.
authors.forename: Haruo
authors.initials: H
authors.lastname: Shintaku
keywords: Cell culture; Glucocorticoids; Neural progenitor cell; Proliferation; iPSC