微生理系统(MPS)是能够模拟组织微环境的2D或3D多细胞构建体。最新的模型包括一系列的技术,包括各种细胞类型的共培养,支架和细胞外基质材料的利用,灌注系统,3D培养方法,3D生物打印,器官芯片技术,和组织结构的检查。在过去的十年中,已经出现了几种人脑3D培养物或脑MPS(BMPS)。这些类器官或球体是源自诱导多能细胞或胚胎干细胞的3D培养系统,其含有神经元和神经胶质群体,并概括人脑的结构和生理方面。BMPS最近已被引入神经感染性疾病的研究和建模中,并已被证明可用于建立病毒感染的神经嗜性。感染所需的细胞-病原体相互作用,评估细胞病理学影响,基因组和蛋白质组谱,和筛选治疗化合物。在这里,我们回顾了神经传染病中使用的类器官的不同方法,包括球体,引导和非引导方案以及含有小胶质细胞和血脑屏障的模型,它们的具体应用,和限制。该综述概述了包括寨卡在内的特定感染的现有模型,登革热,JC病毒,日本脑炎,麻疹,疱疹,SARS-CoV2和流感病毒等,并在疾病和抗病毒剂筛选的建模中提供有用的概念。
Microphysiological systems (MPS) are 2D or 3D multicellular constructs able to mimic tissue microenvironments. The latest models encompass a range of techniques, including co-culturing of various cell types, utilization of scaffolds and extracellular matrix materials, perfusion systems, 3D culture methods, 3D bioprinting, organ-on-a-chip technology, and examination of tissue structures. Several human brain 3D cultures or brain MPS (BMPS) have emerged in the last decade. These organoids or spheroids are 3D culture systems derived from induced pluripotent cells or embryonic stem cells that contain neuronal and glial populations and recapitulate structural and physiological aspects of the human brain. BMPS have been introduced recently in the
study and modeling of neuroinfectious diseases and have proven to be useful in establishing neurotropism of viral infections, cell-pathogen interactions needed for infection, assessing cytopathological effects, genomic and proteomic profiles, and screening therapeutic compounds. Here we review the different methodologies of organoids used in neuroinfectious diseases including spheroids, guided and unguided protocols as well as microglia and blood-brain barrier containing models, their specific applications, and limitations. The review provides an overview of the models existing for specific infections including Zika, Dengue, JC virus, Japanese encephalitis, measles, herpes, SARS-CoV2, and influenza viruses among others, and provide useful concepts in the modeling of disease and antiviral agent screening.