Cantley William, Du Chuang, Lomoio Selene, DePalma Thomas, Peirent Emily, Kleinknecht Dominic, Hunter Martin, Tang-Schomer Min, Tesco Giuseppina, Kaplan David L
Department of Cell, Molecular and Developmental Biology, Sackler School, Tufts University, Boston, MA.
Department of Biomedical Engineering, Tufts University, Medford, MA.
ACS Biomater Sci Eng. 2018 Dec 10;4(12):4278-4288. doi: 10.1021/acsbiomaterials.8b00622. Epub 2018 Oct 1.
Three-dimensional in vitro cell culture models, particularly for the central nervous system, allow for the exploration of mechanisms of organ development, cellular interactions, and disease progression within defined environments. Here we describe the development and characterization of three-dimensional tissue models that promote the differentiation and long-term survival of functional neural networks. These tissue cultures show diverse cell populations including neurons and glial cells (astrocytes) interacting in 3D with spontaneous neural activity confirmed through electrophysiological recordings and calcium imaging over at least 8 months. This approach allows for the direct integration of pluripotent stem cells into the 3D construct bypassing early neural differentiation steps (embryoid bodies and neural rosettes), which streamlines the process while also providing a system that can be manipulated to support a variety of experimental applications. This tissue model has been tested in stem cells derived from healthy individuals as well as Alzheimer's and Parkinson's disease patients, with similar growth and gene expression responses indicating potential use in the modeling of disease states related to neurodegenerative diseases.
三维体外细胞培养模型，尤其是针对中枢神经系统的模型，能够在特定环境中探索器官发育机制、细胞间相互作用以及疾病进展情况。在此，我们描述了促进功能性神经网络分化和长期存活的三维组织模型的开发与特性。这些组织培养物显示出包括神经元和神经胶质细胞（星形胶质细胞）在内的多种细胞群体，它们在三维空间中相互作用，通过电生理记录和钙成像证实至少在8个月内具有自发神经活动。这种方法允许将多能干细胞直接整合到三维构建体中，绕过早期神经分化步骤（胚状体和神经玫瑰花结），这简化了过程，同时还提供了一个可操控以支持各种实验应用的系统。这种组织模型已在源自健康个体以及阿尔茨海默病和帕金森病患者的干细胞中进行了测试，相似的生长和基因表达反应表明其在与神经退行性疾病相关的疾病状态建模中具有潜在用途。
