Functional brain region-specific neural spheroids for modeling neurological diseases and therapeutics screening.
Commun Biol
; 6(1): 1211, 2023 11 28.
Article
en En
| MEDLINE
| ID: mdl-38017066
ABSTRACT
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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Células Madre Pluripotentes Inducidas
Límite:
Humans
Idioma:
En
Revista:
Commun Biol
Año:
2023
Tipo del documento:
Article
País de afiliación:
Estados Unidos