Engineering of midbrain organoids containing long-lived dopaminergic neurons

Article Article scientifique Article Engineering of midbrain organoids containing long-lived dopaminergic neurons eng 2014 author Tieng Caulet Vannary author Stoppini Luc 25479 author Villy Sabrina 663512 author Fathi Marc 565078 author Dubois-Dauphin Michel 21885 author Krause Karl-Heinz 23022 1535-1547 10.1089/scd.2013.0442 24576173 1547-3287 The possibility to generate dopaminergic (DA) neurons from pluripotent stem cells represents an unlimited source of material for tissue engineering and cell therapy for neurodegenerative disease. We set up a protocol based on the generation of size-calibrated neurospheres for a rapid production (3 weeks) of a high amount of DA neurons (>60%) oriented toward a midbrain-like phenotype, characterized by the expression of FOXA2, LMX1A, tyrosine hydroxylase (TH), NURR1, and EN1. By using γ-secretase inhibitors and varying culture time of neurospheres, we controlled maturation and cellular composition of a three-dimensional (3D) engineered nervous tissue (ENT). ENT contained neurons and glial cells expressing various markers of maturity, such as synaptophysin, neuronal nuclei-specific protein (NeuN), and glial fibrillary acidic protein (GFAP), and were electrophysiologically active. We found that 3-week-old neurospheres were optimal to generate 3D tissue containing DA neurons with typical A9 morphology. ENT generated from 4-week-old neurospheres launched glial cell type since astrocytes and myelin could be detected massively at the expense of TH-immunoreactive neurons. All γ-secretase inhibitors were not equivalent; compound E was more efficient than DAPT in generating DA neurons. This DA tissue provides a tool for drug screening, and toxicology. It should also become a useful biomaterial for studies on Parkinson's disease. Cells, Cultured Dopaminergic Neurons/physiology Embryonic Stem Cells Humans Induced Pluripotent Stem Cells Mesencephalon/cytology Organoids/cytology Receptors, Notch/metabolism Spheroids, Cellular/cytology Tissue Engineering Dewey 615 Dewey 616.07 31 Section des sciences pharmaceutiques 17 137 Département de pathologie et immunologie 21F false 38 Radicaux libres et cellules souches embryonnaires 60 Stem cells and development 23 13 a5b52e2d-a496-437e-867e-b9812c0acf23 Article (Published version) Public engineering.pdf 2391341 application/pdf openAccess Faculté des sciences / Section des sciences pharmaceutiques Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie

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Engineering of midbrain organoids containing long-lived dopaminergic neurons	Stem cells and development			2014	785	1,024

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Villy, Sabrina