Zhang Shu-Yuan, Zhao Juan, Ni Jun-Jun, Li Hui, Quan Zhen-Zhen, Qing Hong
Key Laboratory of Molecular Medicine and Biotherapy in the Ministry of Industry and Information Technology, Department of Biology, School of Life Science, Beijing Institute of Technology, Beijing 100081, China.
Aerospace Medical Center, Aerospace Center Hospital, Beijing 100049, China.
World J Stem Cells. 2022 Jun 26;14(6):393-419. doi: 10.4252/wjsc.v14.i6.393.
Over the past few decades, high-throughput screening (HTS) has made great contributions to new drug discovery. HTS technology is equipped with higher throughput, minimized platforms, more automated and computerized operating systems, more efficient and sensitive detection devices, and rapid data processing systems. At the same time, neurogenesis is gradually becoming important in establishing models to investigate the mechanisms of neural disease or deve lopmental processes. However, challenges remain in generating more mature and functional neurons with specific subtypes and in establishing robust and standardized three-dimensional (3D) models with neural cells cultured in 3D matrices or organoids representing specific brain regions. Here, we review the applications of HTS technologies on neurogenesis, especially aiming at identifying the essential genes, chemical small molecules and adaptive microenvironments that hold great prospects for generating functional neurons or more reproductive and homogeneous 3D organoids. We also discuss the developmental tendency of HTS technology, , so-called next-generation screening, which utilizes 3D organoid-based screening combined with microfluidic devices to narrow the gap between models and situations both physiologically and pathologically.
在过去几十年中,高通量筛选(HTS)对新药发现做出了巨大贡献。HTS技术具有更高的通量、最小化的平台、更自动化和计算机化的操作系统、更高效和灵敏的检测设备以及快速的数据处理系统。同时,神经发生在建立研究神经疾病机制或发育过程的模型中逐渐变得重要。然而,在生成具有特定亚型的更成熟和功能性神经元以及建立用三维(3D)基质或代表特定脑区的类器官培养的神经细胞的强大且标准化的三维(3D)模型方面仍然存在挑战。在这里,我们综述了HTS技术在神经发生方面的应用,特别是旨在鉴定对于生成功能性神经元或更具增殖性和同质性的3D类器官具有巨大前景的关键基因、化学小分子和适应性微环境。我们还讨论了HTS技术的发展趋势,即所谓的下一代筛选,它利用基于3D类器官的筛选与微流控设备相结合,以缩小模型与生理和病理状况之间的差距。