Rational Design and Acoustic Assembly of Human Cerebral Cortex-Like Microtissues from hiPSC-Derived Neural Progenitors and Neurons.
Alzheimer's disease
acoustic bioassembly
biofabrication
cerebral cortex-like microtissues
human-relevant histotypic models
Journal
Advanced materials (Deerfield Beach, Fla.)
ISSN: 1521-4095
Titre abrégé: Adv Mater
Pays: Germany
ID NLM: 9885358
Informations de publication
Date de publication:
Aug 2023
Aug 2023
Historique:
revised:
02
05
2023
received:
16
11
2022
medline:
14
8
2023
pubmed:
12
5
2023
entrez:
12
5
2023
Statut:
ppublish
Résumé
Development of biologically relevant and clinically relevant human cerebral cortex models is demanded by mechanistic studies of human cerebral cortex-associated neurological diseases and discovery of preclinical neurological drug candidates. Here, rational design of human-sourced brain-like cortical tissue models is demonstrated by reverse engineering and bionic design. To implement this design, the acoustic assembly technique is employed to assemble hiPSC-derived neural progenitors and neurons separately in a label-free and contact-free manner followed by subsequent neural differentiation and culture. The generated microtissues encapsulate the neuronal microanatomy of human cerebral-cortex tissue that contains six-layered neuronal architecture, a 400-µm interlayer distance, synaptic connections between interlayers, and neuroelectrophysiological transmission. Furthermore, these microtissues are infected with herpes simplex virus type I (HSV-1) virus, and the HSV-induced pathogenesis associated with Alzheimer's disease is determined, including neuron loss and the expression of Aβ. Overall, a high-fidelity human-relevant in vitro histotypic model is provided for the cerebral cortex, which will facilitate wide applications in probing the mechanisms of neurodegenerative diseases and screening the candidates for neuroprotective agents.
Identifiants
pubmed: 37170683
doi: 10.1002/adma.202210631
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2210631Subventions
Organisme : National Natural Science Foundation of China
ID : NSFC 82272173
Organisme : Applied Foundational Research Program of Wuhan Municipal Science and Technology Bureau
ID : 2018010401011296
Informations de copyright
© 2023 Wiley-VCH GmbH.
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