A functional hiPSC-cortical neuron differentiation and maturation model and its application to neurological disorders.
Stem Cell Reports
; 17(1): 96-109, 2022 01 11.
Article
em En
| MEDLINE
| ID: mdl-34942087
ABSTRACT
The maturation and functional characteristics of human induced pluripotent stem cell (hiPSC)-cortical neurons has not been fully documented. This study developed a phenotypic model of hiPSC-derived cortical neurons, characterized their maturation process, and investigated its application for disease modeling with the integration of multi-electrode array (MEA) technology. Immunocytochemistry analysis indicated early-stage neurons (day 21) were simultaneously positive for both excitatory (vesicular glutamate transporter 1 [VGlut1]) and inhibitory (GABA) markers, while late-stage cultures (day 40) expressed solely VGlut1, indicating a purely excitatory phenotype without containing glial cells. This maturation process was further validated utilizing patch clamp and MEA analysis. Particularly, induced long-term potentiation (LTP) successfully persisted for 1 h in day 40 cultures, but only achieved LTP in the presence of the GABAA receptor antagonist picrotoxin in day 21 cultures. This system was also applied to epilepsy modeling utilizing bicuculline and its correction utilizing the anti-epileptic drug valproic acid.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Diferenciação Celular
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Neurogênese
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Células-Tronco Pluripotentes Induzidas
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Neurônios
Tipo de estudo:
Etiology_studies
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Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article