神经科学
大脑皮层
人脑
皮质(解剖学)
祖细胞
单纯疱疹病毒
合理设计
材料科学
生物
纳米技术
干细胞
细胞生物学
病毒学
病毒
作者
Jibo Wang,Haowen Qiao,Zhenyan Wang,Zhao Wen,Tao Chen,Bin Li,Lili Zhu,Sihan Chen,Long-Jun Gu,Ying Wu,Zhentao Zhang,Lin-Lin Bi,Pu Chen
标识
DOI:10.1002/adma.202210631
摘要
Abstract 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 A β . 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.
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