Dingle Yu-Ting L, Boutin Molly E, Chirila Anda M, Livi Liane L, Labriola Nicholas R, Jakubek Lorin M, Morgan Jeffrey R, Darling Eric M, Kauer Julie A, Hoffman-Kim Diane
1 Department of Molecular Pharmacology, Physiology, and Biotechnology, Brown University , Providence, Rhode Island.
2 Center for Biomedical Engineering, Brown University , Providence, Rhode Island.
Tissue Eng Part C Methods. 2015 Dec;21(12):1274-83. doi: 10.1089/ten.TEC.2015.0135. Epub 2015 Oct 6.
There is a high demand for in vitro models of the central nervous system (CNS) to study neurological disorders, injuries, toxicity, and drug efficacy. Three-dimensional (3D) in vitro models can bridge the gap between traditional two-dimensional culture and animal models because they present an in vivo-like microenvironment in a tailorable experimental platform. Within the expanding variety of sophisticated 3D cultures, scaffold-free, self-assembled spheroid culture avoids the introduction of foreign materials and preserves the native cell populations and extracellular matrix types. In this study, we generated 3D spheroids with primary postnatal rat cortical cells using an accessible, size-controlled, reproducible, and cost-effective method. Neurons and glia formed laminin-containing 3D networks within the spheroids. The neurons were electrically active and formed circuitry through both excitatory and inhibitory synapses. The mechanical properties of the spheroids were in the range of brain tissue. These in vivo-like features of 3D cortical spheroids provide the potential for relevant and translatable investigations of the CNS in vitro.
对于用于研究神经系统疾病、损伤、毒性和药物疗效的中枢神经系统（CNS）体外模型有很高的需求。三维（3D）体外模型可以弥合传统二维培养和动物模型之间的差距，因为它们在一个可定制的实验平台中呈现出类似体内的微环境。在不断扩展的各种复杂3D培养物中，无支架、自组装球体培养避免了引入外来材料，并保留了天然细胞群体和细胞外基质类型。在本研究中，我们使用一种可及、尺寸可控、可重复且经济高效的方法，用新生大鼠原代皮质细胞生成了3D球体。神经元和神经胶质细胞在球体内形成了含层粘连蛋白的3D网络。神经元具有电活性，并通过兴奋性和抑制性突触形成回路。球体的力学性能在脑组织范围内。3D皮质球体的这些类似体内的特征为体外进行相关且可转化的CNS研究提供了潜力。
