Human Neurospheroid Arrays for In Vitro Studies of Alzheimer's Disease.
Sci Rep
; 8(1): 2450, 2018 02 05.
Article
em En
| MEDLINE
| ID: mdl-29402979
ABSTRACT
Neurospheroids are commonly used for in vitro disease modeling and drug screening. However, the heterogeneity in size of the neurospheroids mixtures available through current methods limits their utility when employed for basic mechanistic studies of neurodegenerative diseases or screening for new interventions. Here, we generate neurospheroids from immortalized neural progenitor cells and human induced pluripotent stem cells that are uniform in size, into large-scale arrays. In proof of concept experiments, we validate the neurospheroids array as a sensitive and robust tool for screening compounds over extended time. We show that when suspended in three-dimensional extracellular matrix up to several weeks, the stem cell-derived neurospheroids display extensive neurite outgrowth and extend thick bundles of dendrites outward. We also cultivate genetically-engineered stem cell-derived neurospheroids with familial Alzheimer's disease mutations for eight weeks in our microarray system. Interestingly, we observed robust accumulation of amyloid-ß and phosphorylated tau, key hallmarks of Alzheimer's disease. Overall, our in vitro model for engineering neurospheroid arrays is a valuable tool for studying complex neurodegenerative diseases and accelerating drug discovery.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Peptídeos beta-Amiloides
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Proteínas tau
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Esferoides Celulares
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Análise Serial de Tecidos
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Engenharia Celular
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Neurônios
Limite:
Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article