Abstract
In the process of constructing engineered neural tissues, we often use mixed primary neural cells, which contain microglia in the cell culture. However, the role that microglia play in the construction of engineered neural tissue has not been well studied. Here, we generated three-dimensional (3D) engineered neural tissues by silk fibroin/collagen composite scaffolds and primary mixed cortical cells. We depleted microglial cells by magnetic separation. Then, we analyzed the neural growth, development, mature and synapse-related gene, and protein expressions compared with the control engineered neural tissues with the microglia-depleted engineered neural tissues. We found that the engineered neural tissues constructed by magnetic separation to remove microglia showed a decrease in the number of synaptic proteins and mature neurons. These findings link microglia to neuron and synaptic maturation and suggest the importance of microglia in constructing engineered neural tissues in vitro.
Highlights
Most of the in vitro approaches for constructing neuronal networks are based on twodimensional (2D) cultures, which cannot recapitulate three-dimensional (3D) organizations, cell– cell interaction, or their network functions in vivo (Swistowski et al, 2010; Yang et al, 2016; Martin et al, 2018)
We demonstrated that the maturation of neurons and synapse development were decreased in the microglia-depleted 3D tissues group compared with the control group
We mainly studied the role of microglia in the construction of 3D tissue-engineered neural tissues
Summary
Most of the in vitro approaches for constructing neuronal networks are based on twodimensional (2D) cultures, which cannot recapitulate three-dimensional (3D) organizations, cell– cell interaction, or their network functions in vivo (Swistowski et al, 2010; Yang et al, 2016; Martin et al, 2018). In vitro methods to construct 3D neuronal networks that mimic both the structures and functions of neural tissues have been pursued by researchers in various fields, such as neural tissue engineering, neurodegenerative disease studies, and artificial intelligence. Silk protein has received recent attention for neural tissue engineering applications due to its excellent biocompatibility, controllable degradability, controllable mechanical properties, and the ability to be processed into multiple material forms (Kasoju and Bora, 2012; Kundu et al, 2013; Abbott et al, 2016; Huang et al, 2018). The construction of the bioengineered neural tissues based on the silk fibroin (SF)–collagen composite scaffold can recapitulate functional neural networks (Tang-Schomer et al, 2014; Chwalek et al, 2015a,b)
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