Department of Electrical and Computer Engineering, Lehigh University, Bethlehem, PA, USA.
Department of Bioengineering, Lehigh University, Bethlehem, PA, USA.
Commun Biol. 2021 May 17;4(1):587. doi: 10.1038/s42003-021-02104-2.
Aggregation and self-sorting of cells in three dimensional cultures have been described for non-neuronal cells. Despite increased interest in engineered neural tissues for treating brain injury or for modeling neurological disorders in vitro, little data is available on collective cell movements in neuronal aggregates. Migration and sorting of cells may alter these constructs' morphology and, therefore, the function of their neural circuitry. In this work, linear, adhered rat and human 3D neuronal-astrocyte cultures were developed to enable the study of aggregation and sorting of these cells. An in silico model of the contraction, clustering, and cell sorting in the 3D cultures was also developed. Experiments and computational modeling showed that aggregation was mainly a neuron mediated process, and formation of astrocyte-rich sheaths in 3D cultures depended on differential attraction between neurons and astrocytes. In silico model predicted formation of self-assembled neuronal layers in disk-shaped 3D cultures. Neuronal activity patterns were found to correlate with local morphological differences. This model of neuronal and astrocyte aggregation and sorting may benefit future design of neuronal constructs.
细胞在三维培养中的聚集和自分类在非神经元细胞中已有描述。尽管人们对用于治疗脑损伤或在体外模拟神经疾病的工程化神经组织越来越感兴趣，但关于神经元聚集物中细胞的集体运动的数据却很少。细胞的迁移和分类可能会改变这些结构的形态，从而改变其神经回路的功能。在这项工作中，开发了线性、粘附的大鼠和人 3D 神经元-星形胶质细胞培养物，以能够研究这些细胞的聚集和分类。还开发了 3D 培养物中收缩、聚类和细胞分类的计算模型。实验和计算模型表明，聚集主要是神经元介导的过程，3D 培养物中富含星形胶质细胞的鞘的形成取决于神经元和星形胶质细胞之间的差异吸引力。计算模型预测在盘状 3D 培养物中形成自组装的神经元层。发现神经元活动模式与局部形态差异相关。这种神经元和星形胶质细胞聚集和分类的模型可能有助于未来神经元构建体的设计。
