3D Human Tumor Tissues Cultured in Dynamic Conditions as Alternative In Vitro Disease Models

Abstract

The slow knowledge progression about cancer disease and the high drug clinical failure are mainly due to the inadequacy of the simplistic pre-clinical in vitro and in vivo animal tumor models. To overpass these limits, in recent years many 3D matrix-based cell cultures have been proposed as challenging alternatives, since they allow to better recapitulate the in vitro cells-cells and cells-matrix reciprocal interactions in a more physiological context. Among many natural polymers, alginate has been adopted as an extracellular matrix surrogate to mimic the 3D spatial organization. After their expansion, cancer cells are suspended in an alginate solution and dropped within a crosslinking solution enabling gelification. The result is the generation of a 3D hydrogel embedding a single cell suspension: Cells are equally distributed throughout the gel, and they are free to proliferate generating clonal spheroids. Moreover, according to the hydrogel matrix stiffness that can be easily tuned, tumor cells can spread within the 3D structure and migrate outside, where they may become circulating tumor cells and infiltrate secondary tumor sites when these 3D tumor tissues are cultured in a fluid dynamic environment (i.e., organ on chip).

Keywords: 3D culture; Alginate; Cell-embedding; Fluid dynamic culture; Physiological model: MIVO®; Tumor model.