Using Bioprinting to Create Better 3D Tumor Models3 Comments
The generation of relevant 3D in vitro tumor models presents many challenges, but they are increasingly recognized as one of the best preclinical drug-screening platforms and an improved method to study cancer in controlled conditions in the laboratory, due to their enormous potential for recapitulating the appropriate three-dimensional and physiological features of human tumor tissues.
Traditional methods in which cancer cells are grown in a monolayer in two dimensions result in flat cells where there is no opportunity for cellular contact on all sides. This modifies cellular function due to loss of these interactions, altered cell polarity, and changes in cell shape resulting in a deficient model for understanding cancer biology or establishing appropriate antitumoral therapies. A high number of drugs have been shown to be effective in killing cancer cell monolayers, only to go on to fail in demonstrating any relevance when reaching the clinical stage. However, even though 2D culture models lack realistic complexity, the alternative animal models are very expensive and time consuming and often fail to replicate in vivo human tumor biology. Furthermore, in animal xenografts human cancer cells are usually transplanted to sites in the mouse that are convenient for experimental reasons but unfortunately do not necessarily reflect the original microenvironment of the parent tumor. Thus, 3D in vitro models can be found to be much more realistic than such animal models.
The main challenge and a priority aspect for relevant in vitro 3D models is the ability to mimic the complexity of the tumor microenvironment appropriately. In order to reproduce the complex interactions between tumor cells, stromal cells and ECM, and replicate the typical tumor compartmentalization in a precise manner, cancer cells would need to be grown in a sphere-shaped organoid, and would have to be combined with biomaterials that allow tunability of both the setup and experimental handling.
Whilst there are several 3D cell culture techniques available for the generation of tumor spheroids including hanging-drop and non-adherent surface technologies, bioprinting techniques for the generation of tumor spheroids are receiving increasing attention due to their ability to incorporate appropriate tumor architecture in a precise and controlled manner. 3D printing multiple cell types into specific scaffolds can help the generation of improved tumor organoids in which cancer cells are able to self-organize, grow, secrete their extracellular matrix and behave as they would in vivo, thus accurately representing the tumor microenvironment.
Three-dimensional bioprinting of live human cells has shown that effective in vitro replication of tumor biology is achievable. Several recent articles outline current developments in the use of bioprinted models used in cancer research, opening up a new frontier for the understanding of tumor biology and advancement of cancer therapies.
Image source: Charbe N. et al. 3D bio-printing in oncology research. WJCO, 2017
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