Development of 3-dimensional cell culture for integrated modelling of cells and tissues

3D细胞培养允许研究处于活体状态的细胞，使3D细胞系更真实地反映生理细胞环境。这在一定程度上是由于整个细胞表面暴露，允许激活信号通路和其他细胞过程。正是由于这些原因，3D细胞系在研究基因表达、细胞凋亡、药物摄取和药物毒性等过程时是首选的。3D培养方法主要有两种：支架技术(支架、仿生支架和水凝胶)和无支架技术(生物反应器、磁悬浮和3D生物打印)。这些细胞培养方法使细胞的行为与活体条件下的情况相似(在细胞通讯和细胞外基质的发展方面)，产生更准确的组织细胞组成的表示，并采用与活体相似的极性(仅在2D中实现部分极性)。它们还可以研究肿瘤的特征，如休眠、缺氧和抗凋亡行为，最终赋予细胞更大的稳定性和更长的寿命。高含量筛选将以光片显微镜的形式进行；允许研究细胞对各种因素的三维表型反应。光片显微镜的优点是减少了光漂白，而且几乎没有光毒效应，可以延长成像时间。它还允许在亚细胞分辨率下对整个样本进行成像，使其成为执行3D细胞培养的高含量筛选时的强大工具。

3D cell culture allows the study of cells in an in vivo like state, making 3D cell lines a truer reflection of the physiological cell environment. This is due in part to the exposure of the whole cell surface, allowing the activation of signalling pathways and other cellular processes. It is for these reasons that 3D cell lines are preferred when studying processes such as gene expression, apoptosis, drug uptake and drug toxicity. There are two main types of 3D culture methods: Scaffold techniques (Scaffolds, biomimetic scaffolds and hydrogels) and scaffold-free techniques (bioreactors, magnetic levitation and 3D bioprinting). These cell culture methods allow cells to; behave akin to those in in vivo conditions (in terms of cellular communication and the development of the extracellular matrix), produce a more accurate representation of the cellular composition of tissues and adopt a polarity like in vivo (only achieve partial polarity in 2D). They also allow the study of tumour characteristics such as dormancy, hypoxia and anti-apoptotic behaviour and finally give the cells greater stability and a longer lifespan. High content screening will be executed in the form of light sheet microscopy; allowing the study of the cells phenotypic response to a variety of factors in 3-dimensions. Light sheet microscopy offers the advantages of reduced photo-bleaching as well as virtually no phototoxic effects permitting imaging for extended time periods. It also allows imaging of the whole sample at sub-cellular resolution making it a powerful tool when performing high content screening of 3D cell cultures.