Division of Cell Biology and Imaging, National Institute for Biological Standards and Control, South Mimms, Potters Bar, Hertfordshire, UK.
Adv Exp Med Biol. 2012;745:1-13. doi: 10.1007/978-1-4614-3055-1_1.
The ideal features of a cell culture system for in vitro investigation depend on what questions the system is to address. However, in general, highly valuable systems will replicate the characteristics and more specifically, the responses, of normal human tissues. Systems that can faithfully replicate different tissue types provide tremendous potential value for in vitro research and have been the subject of much research effort in this area over many years. Furthermore, a range of such systems that could mimic key genetic variations or diseases would have special value for toxicology and drug discovery. In the pursuit of such model systems, there are a number of significant practical issues to consider for their application, which includes ability to deliver with ease, the required quantities of cells at the time needed. In addition any cell culture assay will need to be robust and reliable and provide readily interpreted and quantified endpoints. Other general criteria for cell culture systems include scalability to provide the very large cell numbers that may be required for high throughput systems, with a high degree of reliability and reproducibility. The amenability of the cell culture for down-scaling may also be important, to permit the use of very small test samples (e.g., in 96-well arrays), even down to the level of single cell analysis. This chapter explores the range of new cell culture systems for scaling up cell cultures that will be needed for high throughput toxicology and drug discovery assays. It also reviews the increasing range of novel systems that enable high content analysis from small cell numbers or even single cells. The hopes and challenges for the use of human stem cell lines are also investigated in comparison with the range of eukaryotic cells types currently in use in toxicology.
体外研究用细胞培养系统的理想特征取决于该系统需要解决哪些问题。然而，一般来说，非常有价值的系统将复制正常人体组织的特征，更具体地说，是其反应。能够忠实地复制不同组织类型的系统为体外研究提供了巨大的潜在价值，多年来一直是该领域大量研究工作的主题。此外，能够模拟关键遗传变异或疾病的此类系统对于毒理学和药物发现将具有特殊价值。在追求这种模型系统的过程中，需要考虑许多重要的实际问题，以将其应用于实际，其中包括能够轻松地提供所需数量的细胞。此外，任何细胞培养测定都需要具有稳健性和可靠性，并提供易于解释和量化的终点。细胞培养系统的其他一般标准包括可扩展性，以提供高通量系统可能需要的大量细胞，具有高度可靠性和可重复性。细胞培养易于缩小规模也可能很重要，以允许使用非常小的测试样本（例如，在 96 孔阵列中），甚至可以达到单细胞分析的水平。本章探讨了用于高通量毒理学和药物发现测定的细胞培养系统的各种新型放大细胞培养系统。它还回顾了越来越多的新型系统，这些系统能够从小细胞数量甚至单个细胞中进行高内涵分析。还比较了人类干细胞系的使用希望和挑战，以及毒理学中目前使用的各种真核细胞类型。
