Comparative performance analysis of human iPSC-derived and primary neural progenitor cells (NPC) grown as neurospheres in vitro.
Fiche publication
Date publication
décembre 2017
Journal
Stem cell research
Auteurs
Membres identifiés du Cancéropôle Est :
Dr EGLY Jean-Marc
Tous les auteurs :
Hofrichter M, Nimtz L, Tigges J, Kabiri Y, Schröter F, Royer-Pokora B, Hildebrandt B, Schmuck M, Epanchintsev A, Theiss S, Adjaye J, Egly JM, Krutmann J, Fritsche E
Lien Pubmed
Résumé
Developmental neurotoxicity (DNT) testing performed in rats is resource-intensive (costs, time, animals) and bears the issue of species extrapolation. Thus, reliable alternative human-based approaches are needed for predicting neurodevelopmental toxicity. Human induced pluripotent stem cells (hiPSCs) represent a basis for an alternative method possibly being part of an alternative DNT testing strategy. Here, we compared two hiPSC neural induction protocols resulting in 3D neurospheres: one using noggin and one cultivating cells in neural induction medium (NIM protocol). Performance of Nestin/SOX2 hiPSC-derived neural progenitor cells (NPCs) was compared to primary human NPCs. Generally, primary hNPCs first differentiate into Nestin and/or GFAP radial glia-like cells, while the hiPSC-derived NPCs (hiPSC-NPC) first differentiate into βIII-Tubulin neurons suggesting an earlier developmental stage of hiPSC-NPC. In the 'Neurosphere Assay', NIM generated hiPSC-NPC produced neurons with higher performance than with the noggin protocol. After long-term differentiation, hiPSC-NPC form neuronal networks, which become electrically active on microelectrode arrays after 85days. Finally, methylmercury chloride inhibits hiPSC-NPC and hNPC migration with similar potencies. hiPSC-NPCs-derived neurospheres seem to be useful for DNT evaluation representing early neural development in vitro. More system characterization by compound testing is needed to gain higher confidence in this method.
Mots clés
Brain development, In vitro, MEA, Stem cell, Testing
Référence
Stem Cell Res. 2017 Dec;25:72-82