Three-Dimensional Neural Spheroid Culture: An In Vitro Model for Cortical Studies

Three-Dimensional Neural Spheroid Culture: An In Vitro Model for Cortical Studies
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DOI:
10.1089/ten.tec.2015.0135
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发表时间:
2015-12-01
影响因子:
3
通讯作者:
Hoffman-Kim, Diane
Hoffman-Kim, Diane
中科院分区:
医学4区
文献类型:
--
作者:
Dingle, Yu-Ting L.;Boutin, Molly E.;Hoffman-Kim, Diane

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中枢神经系统(CNS)的体外模型研究神经系统疾病,损伤,毒性和药物疗效的需求很高。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,因为它们在可定制的实验平台中呈现类似于体内的微环境。在不断扩大的各种复杂的3D培养中,无支架的自组装球体培养避免了外来物质的引入,并保留了天然细胞群和细胞外基质类型。在这项研究中,我们使用一种可访问的,尺寸可控的,可重复的和具有成本效益的方法生成了3D球体与原代出生后大鼠皮质细胞。神经元和胶质细胞在球状体内形成含层粘连蛋白的三维网络。神经元是电活性的,并通过兴奋性和抑制性突触形成电路。球体的力学性能在脑组织范围内。这些在体内的三维皮质球状体的功能提供了潜在的相关和可翻译的研究中枢神经系统在体外。
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.