Three-Dimensional Cell Culture Models of Hepatocellular Carcinoma - a Review.

Abstract

Three-dimensional (3D) cell culture studies are becoming extremely common because of theircapability to mimic tumor architecture, such as cell-cell and cell-ECM interactions, more efficiently than 2Dmonolayer systems. These interactions have important roles in defining the tumor cell behaviors, such asproliferation, differentiation, and most importantly, tumor drug response. This review aims to provide an overview of the methods for 3D tumor spheroid formation to modelhuman tumors, specifically concentrated on studies using hepatocellular carcinoma (HCC) cells. We obtained information from previously published articles. In this review, there is discussion of thescaffold and non-scaffold-based approaches, including hanging drop, bioreactors and 3D bioprinting. The mimicking of the tumor microenvironment (TME) as tumor spheroids could provide avaluable platform for studying tumor biology. Multicellular tumor spheroids are self-assembled cultures of mixedcells (tumor and stromal cells) organized in a 3D arrangement. These spheroids closely mimic the main features ofhuman solid tumors, such as structural organization, central hypoxia, and overall oxygen and nutrient gradients.Hepatocellular carcinoma (HCC) is the most common liver malignancy, and most difficult to overcome because ofits drug resistance and tumor heterogeneity. In order to mimic this highly heterogeneous environment, 3D cellculture systems are needed.