Functional brain region-specific neural spheroids for modeling neurological diseases and therapeutics screening.
Journal
Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179
Informations de publication
Date de publication:
28 Nov 2023
28 Nov 2023
Historique:
received:
03
04
2023
accepted:
14
11
2023
medline:
30
11
2023
pubmed:
29
11
2023
entrez:
28
11
2023
Statut:
epublish
Résumé
3D spheroids have emerged as powerful drug discovery tools given their high-throughput screening (HTS) compatibility. Here, we describe a method for generating functional neural spheroids by cell-aggregation of differentiated human induced pluripotent stem cell (hiPSC)-derived neurons and astrocytes at cell type compositions mimicking specific regions of the human brain. Recordings of intracellular calcium oscillations were used as functional assays, and the utility of this spheroids system was shown through disease modeling, drug testing, and formation of assembloids to model neurocircuitry. As a proof of concept, we generated spheroids incorporating neurons with Alzheimer's disease-associated alleles, as well as opioid use disorder modeling spheroids induced by chronic treatment of a mu-opioid receptor agonist. We reversed baseline functional deficits in each pilot disease model with clinically approved treatments and showed that assembloid activity can be chemogenetically manipulated. Here, we lay the groundwork for brain region-specific neural spheroids as a robust functional assay platform for HTS studies.
Identifiants
pubmed: 38017066
doi: 10.1038/s42003-023-05582-8
pii: 10.1038/s42003-023-05582-8
pmc: PMC10684574
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1211Informations de copyright
© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.
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