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Rat Cortical Oligodendrocyte–Embryonic Motoneuron Co-Culture: An In Vitro Axon-Oligodendrocyte Interaction Model

机译:大鼠皮质脱突胚细胞 - 胚胎运动神经元共同培养:体外轴突 - 少突突键相互作用模型

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摘要

Mechanisms that control the differentiation and function of oligodendrocytes in the central nervous system are complex and involve multiple inputs from the surrounding environment, including localized concentrations of growth factors and the extracellular matrix. Dissection and analysis of these inputs are key to understanding the pathology of central nervous system demyelinating diseases such as multiple sclerosis, where the differentiation of myelinating oligodendrocytes from their precursors underlies the remission phase of the disease. In vitro co-culture models provide a mechanism for the study of factors that regulate differentiation of oligodendrocyte precursors but have been difficult to develop due to the complex nature of central nervous system myelination. This study describes development of an in vitro model that merges a defined medium with a chemically modified substrate to study aspects of myelination in the central nervous system. We demonstrate that oligodendrocyte precursors co-cultured with rat embryonic motoneurons on non-biological substrate (diethylenetriamine trimethoxy-silylpropyldiethylenetriamine), can be induced to differentiate into mature oligodendrocytes that express myelin basic protein, using a serum-free medium. This defined and reproducible model of in vitro myelination could be a valuable tool for the development of treatments for demyelinating diseases such as multiple sclerosis.
机译:控制中枢神经系统中少突胶质细胞的分化和功能的机制很复杂,涉及周围环境的多种输入,包括局部浓度的生长因子和细胞外基质。这些输入的解剖和分析是了解中枢神经系统脱髓鞘疾病(例如多发性硬化症)病理的关键,在该疾病中,髓鞘少突胶质细胞与其前体的分化是疾病缓解阶段的基础。体外共培养模型为研究调节少突胶质前体细胞分化的因素提供了一种机制,但由于中枢神经系统髓鞘化的复杂性而难以开发。这项研究描述了体外模型的开发,该模型将定义的培养基与化学修饰的底物融合在一起,以研究中枢神经系统中髓鞘形成的各个方面。我们证明,与大鼠胚胎运动神经元在非生物底物(二亚乙基三胺三甲氧基-甲硅烷基丙基二亚乙基三胺)上共培养的少突胶质细胞前体,可以被诱导分化成表达髓鞘碱性蛋白的成熟少突胶质细胞,使用无血清培养基。这种确定的,可再现的体外髓鞘形成模型可能是开发脱髓鞘疾病(例如多发性硬化症)的治疗方法的有价值的工具。

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