Zhang Jiangang, Yang Huiyu, Wu Jiaming, Zhang Dingyue, Wang Yu, Zhai Jiliang
Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Departments of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Front Bioeng Biotechnol. 2022 Aug 17;10:953031. doi: 10.3389/fbioe.2022.953031. eCollection 2022.
Central nervous system (CNS) diseases have been a growing threat to the health of humanity, emphasizing the urgent need of exploring the pathogenesis and therapeutic approaches of various CNS diseases. Primary neurons are directly obtained from animals or humans, which have wide applications including disease modeling, mechanism exploration and drug development. However, traditional two-dimensional (2D) monoculture cannot resemble the native microenvironment of CNS. With the increasing understanding of the complexity of the CNS and the remarkable development of novel biomaterials, models have experienced great innovation from 2D monoculture toward three-dimensional (3D) multicellular culture. The scope of this review includes the progress of various models of primary neurons in recent years to provide a holistic view of the modalities and applications of primary neuron models and how they have been connected with the revolution of biofabrication techniques. Special attention has been paid to the interaction between primary neurons and biomaterials. First, a brief introduction on the history of CNS modeling and primary neuron culture was conducted. Next, detailed progress in novel models were discussed ranging from 2D culture, model, spheroid, scaffold-based model, 3D bioprinting model, and microfluidic chip. Modalities, applications, advantages, and limitations of the aforementioned models were described separately. Finally, we explored future prospects, providing new insights into how basic science research methodologies have advanced our understanding of the CNS, and highlighted some future directions of primary neuron culture in the next few decades.
中枢神经系统（CNS）疾病对人类健康的威胁日益增大，这凸显了探索各种中枢神经系统疾病发病机制和治疗方法的迫切需求。原代神经元直接从动物或人类获取，具有广泛应用，包括疾病建模、机制探索和药物研发。然而，传统的二维（2D）单培养无法模拟中枢神经系统的天然微环境。随着对中枢神经系统复杂性的认识不断加深以及新型生物材料的显著发展，模型已从二维单培养向三维（3D）多细胞培养经历了重大创新。本综述的范围包括近年来原代神经元各种模型的进展，以全面了解原代神经元模型的模式和应用，以及它们如何与生物制造技术的变革相联系。特别关注了原代神经元与生物材料之间的相互作用。首先，对中枢神经系统建模和原代神经元培养的历史进行了简要介绍。接下来，讨论了新型模型的详细进展，范围涵盖二维培养、模型、球体、基于支架的模型、三维生物打印模型和微流控芯片。分别描述了上述模型的模式、应用、优点和局限性。最后，我们探索了未来前景，为基础科学研究方法如何增进我们对中枢神经系统的理解提供了新见解，并强调了未来几十年原代神经元培养的一些方向。
