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unige:82443 
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Engineering of midbrain organoids containing long-lived dopaminergic neurons |
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| Published in | Stem Cells and Development. 2014, vol. 23, no. 13, p. 1535-47 | |
| Abstract | 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. | |
| Keywords | 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 | |
| Identifiers | PMID: 24576173 | |
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| Research group | Radicaux libres et cellules souches embryonnaires (60) | |
| Citation (ISO format) | TIENG CAULET, Vannary et al. Engineering of midbrain organoids containing long-lived dopaminergic neurons. In: Stem Cells and Development, 2014, vol. 23, n° 13, p. 1535-47. https://archive-ouverte.unige.ch/unige:82443 |
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