Université Clermont-Auvergne, INRAE, UNH, Unité de Nutrition Humaine, CRNH-Auvergne, 63000 Clermont-Ferrand, France.
Equipe Tumorigénèse Pharmacologie Moléculaire et Anticancéreuse, Faculté des Sciences II, Université Libanaise Fanar, Beyrouth 1500, Liban.
Int J Mol Sci. 2021 Nov 11;22(22):12200. doi: 10.3390/ijms222212200.
The traditional two-dimensional (2D) in vitro cell culture system (on a flat support) has long been used in cancer research. However, this system cannot be fully translated into clinical trials to ideally represent physiological conditions. This culture cannot mimic the natural tumor microenvironment due to the lack of cellular communication (cell-cell) and interaction (cell-cell and cell-matrix). To overcome these limitations, three-dimensional (3D) culture systems are increasingly developed in research and have become essential for tumor research, tissue engineering, and basic biology research. 3D culture has received much attention in the field of biomedicine due to its ability to mimic tissue structure and function. The 3D matrix presents a highly dynamic framework where its components are deposited, degraded, or modified to delineate functions and provide a platform where cells attach to perform their specific functions, including adhesion, proliferation, communication, and apoptosis. So far, various types of models belong to this culture: either the culture based on natural or synthetic adherent matrices used to design 3D scaffolds as biomaterials to form a 3D matrix or based on non-adherent and/or matrix-free matrices to form the spheroids. In this review, we first summarize a comparison between 2D and 3D cultures. Then, we focus on the different components of the natural extracellular matrix that can be used as supports in 3D culture. Then we detail different types of natural supports such as matrigel, hydrogels, hard supports, and different synthetic strategies of 3D matrices such as lyophilization, electrospiding, stereolithography, microfluid by citing the advantages and disadvantages of each of them. Finally, we summarize the different methods of generating normal and tumor spheroids, citing their respective advantages and disadvantages in order to obtain an ideal 3D model (matrix) that retains the following characteristics: better biocompatibility, good mechanical properties corresponding to the tumor tissue, degradability, controllable microstructure and chemical components like the tumor tissue, favorable nutrient exchange and easy separation of the cells from the matrix.
传统的二维（2D）体外细胞培养系统（在平面载体上）长期以来一直用于癌症研究。然而，由于缺乏细胞间通讯（细胞-细胞）和相互作用（细胞-细胞和细胞-基质），该培养系统不能完全转化为临床试验，以理想地代表生理条件。由于缺乏细胞间通讯（细胞-细胞）和相互作用（细胞-细胞和细胞-基质），这种培养不能模拟自然肿瘤微环境。为了克服这些限制，三维（3D）培养系统在研究中得到了越来越多的发展，并且对于肿瘤研究、组织工程和基础生物学研究已经成为必不可少的。由于其模拟组织结构和功能的能力，3D 培养在生物医学领域受到了广泛关注。3D 基质呈现出高度动态的框架，其成分被沉积、降解或修饰以描绘功能，并提供一个平台，细胞附着在该平台上执行其特定功能，包括粘附、增殖、通讯和凋亡。到目前为止，各种类型的模型都属于这种培养：要么是基于天然或合成附着基质的培养，用于设计 3D 支架作为生物材料以形成 3D 基质，要么是基于非附着和/或无基质基质以形成球体。在这篇综述中，我们首先总结了 2D 和 3D 培养之间的比较。然后，我们专注于天然细胞外基质的不同成分，这些成分可以用作 3D 培养的支架。然后，我们详细介绍了不同类型的天然支架，如基质胶、水凝胶、硬支架，以及不同的 3D 基质的合成策略，如冻干、静电纺丝、立体光刻、微流控，通过引用它们各自的优缺点。最后，我们总结了生成正常和肿瘤球体的不同方法，引用了它们各自的优缺点，以获得理想的 3D 模型（基质），保留以下特征：更好的生物相容性、与肿瘤组织相匹配的良好机械性能、可降解性、可控的微结构和化学成分、有利于营养物质交换和细胞与基质的易于分离。
