Effect of prolonged differentiation on functional maturation of human pluripotent stem cell-derived neuronal cultures.

Autor:	Paavilainen T; NeuroGroup, BioMediTech and Faculty of Medicine and Life Sciences, University of Tampere, Arvo Ylpön katu 34, 33520 Tampere, Finland., Pelkonen A; NeuroGroup, BioMediTech and Faculty of Medicine and Life Sciences, University of Tampere, Arvo Ylpön katu 34, 33520 Tampere, Finland., Mäkinen ME; NeuroGroup, BioMediTech and Faculty of Medicine and Life Sciences, University of Tampere, Arvo Ylpön katu 34, 33520 Tampere, Finland., Peltola M; NeuroGroup, BioMediTech and Faculty of Medicine and Life Sciences, University of Tampere, Arvo Ylpön katu 34, 33520 Tampere, Finland., Huhtala H; Faculty of Social Sciences, University of Tampere, Arvo Ylpön katu 34, 33520 Tampere, Finland., Fayuk D; NeuroGroup, BioMediTech and Faculty of Medicine and Life Sciences, University of Tampere, Arvo Ylpön katu 34, 33520 Tampere, Finland., Narkilahti S; NeuroGroup, BioMediTech and Faculty of Medicine and Life Sciences, University of Tampere, Arvo Ylpön katu 34, 33520 Tampere, Finland. Electronic address: susanna.narkilahti@uta.fi.
Jazyk:	angličtina
Zdroj:	Stem cell research [Stem Cell Res] 2018 Mar; Vol. 27, pp. 151-161. Date of Electronic Publication: 2018 Jan 31.
DOI:	10.1016/j.scr.2018.01.018
Abstrakt:	Long-term neural differentiation of human pluripotent stem cells (hPSCs) is associated with enhanced neuronal maturation, which is a necessity for creation of representative in vitro models. It also induces neurogenic-to-gliogenic fate switch, increasing proportion of endogenous astrocytes formed from the common neural progenitors. However, the significance of prolonged differentiation on the neural cell type composition and functional development of hPSC-derived neuronal cells has not been well characterized. Here, we studied two hPSC lines, both of which initially showed good neuronal differentiation capacity. However, the propensity for endogenous astrogenesis and maturation state after extended differentiation varied. Live cell calcium imaging revealed that prolonged differentiation facilitated maturation of GABAergic signaling. According to extracellular recordings with microelectrode array (MEA), neuronal activity was limited to fewer areas of the culture, which expressed more frequent burst activity. Efficient maturation after prolonged differentiation also promoted organization of spontaneous activity by burst compaction. These results suggest that although prolonged neural differentiation can be challenging, it has beneficial effect on functional maturation, which can also improve transition to different neural in vitro models and applications. (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze:	MEDLINE
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