Generation of Interconnected Neural Clusters in Multiscale Scaffolds from Human-Induced Pluripotent Stem Cells - Processus d'activation sélective par transfert d'énergie uni-électronique ou radiatif Accéder directement au contenu
Article Dans Une Revue ACS Applied Materials & Interfaces Année : 2021

Generation of Interconnected Neural Clusters in Multiscale Scaffolds from Human-Induced Pluripotent Stem Cells

Résumé

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.
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hal-03442115 , version 1 (26-11-2021)

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Boxin Huang, Juan Peng, Xiaochen Huang, Feng Liang, Li Wang, et al.. Generation of Interconnected Neural Clusters in Multiscale Scaffolds from Human-Induced Pluripotent Stem Cells. ACS Applied Materials & Interfaces, 2021, 13 (47), pp.55939-55952. ⟨10.1021/acsami.1c18465⟩. ⟨hal-03442115⟩
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