Generation of Interconnected Neural Clusters in Multiscale Scaffolds from Human-Induced Pluripotent Stem Cells.
ACS Appl Mater Interfaces
; 13(47): 55939-55952, 2021 Dec 01.
Article
en En
| MEDLINE
| ID: mdl-34788005
ABSTRACT
The development of in vitro neural networks depends to a large extent on the scaffold properties, including the scaffold stiffness, porosity, and dimensionality. Herein, we developed a method to generate interconnected neural clusters in a multiscale scaffold consisting of a honeycomb microframe covered on both sides with a monolayer of cross-linked gelatin nanofibers. Cortical neural precursor cells were first produced from human-induced pluripotent stem cells and then loaded into the scaffold for a long period of differentiation toward cortical neural cells. As a result, neurons and astrocytes self-organized in the scaffold to form clusters in each of the honeycomb compartments with remarkable inter-cluster connections. These cells highly expressed neuron- and astrocyte-specific proteins, including NF200, tau, synapsin I, and glial fibrillary acidic protein, and showed spatially correlated neural activities. Two types of neural clusters, that is, spheroid-like and hourglass-like clusters, were found, indicating the complexity of neural-scaffold interaction and the variability of three-dimensional neural organization. Furthermore, we incorporated a reconstituted basement membrane into the scaffold and performed co-culture of the neural network with brain microvascular endothelial cells. As a proof of concept, an improved neurovascular unit model was tested, showing large astrocytic end-feet on the back side of the endothelium.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Redes Neurales de la Computación
/
Células Madre Pluripotentes Inducidas
/
Células-Madre Neurales
Límite:
Humans
Idioma:
En
Revista:
ACS Appl Mater Interfaces
Asunto de la revista:
BIOTECNOLOGIA
/
ENGENHARIA BIOMEDICA
Año:
2021
Tipo del documento:
Article
País de afiliación:
Francia