iPSC-derived three-dimensional brain organoid models and neurotropic viral infections.

iPSC-derived three-dimensional brain organoid models and neurotropic viral infections.
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DOI:
10.1007/s13365-023-01133-3
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发表时间:
2023-04
影响因子:
3.2
通讯作者:
Sariyer, Ilker K.
Sariyer, Ilker K.
中科院分区:
医学4区
文献类型:
--
作者:
Swingler, Michael;Donadoni, Martina;Bellizzi, Anna;Cakir, Senem;Sariyer, Ilker K.

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二十多年来,干细胞研究的进展彻底改变了医学领域。最近,诱导多能干细胞(iPSC)的发现已经允许开发先进的疾病建模和组织工程平台。iPSC是通过表达建立多能性所需的转录因子将成年体细胞重新编程为胚胎样状态而产生的。在中枢神经系统(CNS)的背景下,iPSC具有分化成多种脑细胞类型的潜力,包括神经元、星形胶质细胞、小胶质细胞、内皮细胞和少突胶质细胞。iPSC可用于通过在体外三维(3D)培养中使用构建性方法来产生脑类器官。3D脑类器官建模的最新进展提供了更好地理解疾病进展中细胞与细胞相互作用的途径,特别是嗜神经病毒感染。由于缺乏中枢神经系统细胞网络的多细胞组成,在体外二维培养系统中难以研究嗜神经病毒感染。近年来,3D脑类器官已被首选用于模拟嗜神经病毒疾病,并为更好地理解病毒感染和细胞反应的分子调控提供了宝贵的信息。在这里,我们对iPSC衍生的3D脑类器官培养的最新进展及其在建模主要嗜神经病毒感染(包括HIV-1、HSV-1、JCV、ZIKV、CMV和SARS-CoV 2)中的应用的文献进行了全面综述。
Progress in stem cell research has revolutionized the medical field for more than two decades. More recently, the discovery of induced pluripotent stem cells (iPSCs) has allowed for the development of advanced disease modeling and tissue engineering platforms. iPSCs are generated from adult somatic cells by reprogramming them into an embryonic-like state via the expression of transcription factors required for establishing pluripotency. In the context of the central nervous system (CNS), iPSCs have the potential to differentiate into a wide variety of brain cell types including neurons, astrocytes, microglial cells, endothelial cells, and oligodendrocytes. iPSCs can be used to generate brain organoids by using a constructive approach in three-dimensional (3D) culture in vitro. Recent advances in 3D brain organoid modeling have provided access to a better understanding of cell-to-cell interactions in disease progression, particularly with neurotropic viral infections. Neurotropic viral infections have been difficult to study in two-dimensional culture systems in vitro due to the lack of a multicellular composition of CNS cell networks. In recent years, 3D brain organoids have been preferred for modeling neurotropic viral diseases and have provided invaluable information for better understanding the molecular regulation of viral infection and cellular responses. Here we provide a comprehensive review of the literature on recent advances in iPSC-derived 3D brain organoid culturing and their utilization in modeling major neurotropic viral infections including HIV-1, HSV-1, JCV, ZIKV, CMV, and SARS-CoV2.
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