1 Leads Discovery & Optimization, Bristol-Myers Squibb Company, Princeton, NJ, USA.
SLAS Discov. 2018 Feb;23(2):122-131. doi: 10.1177/2472555217733437. Epub 2017 Sep 28.
Chemotaxis is the directional movement of cells in response to a chemical stimulus and is vital for many physiological processes, including immune responses, tumor metastasis, wound healing, and blood vessel formation. Therefore, modulation of chemotaxis is likely to be of therapeutic benefit. Hence, a high-throughput means to conduct chemotaxis assays is advantageous for lead evaluation and optimization in drug discovery. In this study, we have validated a novel approach for a higher-throughput, label-free, image-based IncuCyte chemotaxis assay encompassing various cell types, including T cells, B cells, mouse Th17, immature and mature dendritic cells, monocyte THP-1, CCRF-CEM, monocytes, neutrophils, macrophages, and MDA-MB-231. These assays enable us to visualize chemotactic cell migration in real time and perform kinetic cell motility studies on an automated platform, thereby allowing us to incorporate the quantitative studies of cell migration behavior into a routine drug discovery screening cascade.
趋化性是细胞对化学刺激的定向运动，对于许多生理过程至关重要，包括免疫反应、肿瘤转移、伤口愈合和血管形成。因此，趋化性的调节可能具有治疗益处。因此，高通量的趋化性测定方法有利于药物发现中的先导评估和优化。在这项研究中，我们验证了一种新的高通量、无标记、基于图像的 IncuCyte 趋化性测定方法，该方法涵盖了各种细胞类型，包括 T 细胞、B 细胞、小鼠 Th17、未成熟和成熟树突状细胞、单核细胞 THP-1、CCRF-CEM、单核细胞、嗜中性粒细胞、巨噬细胞和 MDA-MB-231。这些测定方法使我们能够实时可视化趋化性细胞迁移，并在自动化平台上进行动力学细胞运动研究，从而使我们能够将细胞迁移行为的定量研究纳入常规药物发现筛选级联。
