Development of a microfluidic system for co-culturing multicellular tumor spheroid and vasculature

Abstract

As tumor remains as one of the main causes of death in current society, a wide range of researches is focused on the development of anti-cancer drugs and uncovering the underlying mechanism. However, limitations still exist that most studies are based on the animal model which have different microenvironment compared with human. Moreover, the animal models cannot be monitored in real-time that it remains as an endpoint experiment. Microfluidic system composed of human-derived cells may remedy some of these limitations by recreating more physiologically relevant microenvironment. Since vasculature is crucial for survival and growth of a tumor, co-culture of vasculature with tumor should be thoroughly considered for mimicking tumor microenvironment. Here, we suggest silicon based transparent microfluidic chip model, composed of multicellular tumor spheroid and vascular endothelial cells. Since in-vivo tumor cells are in the form of aggregation or cluster, multicellular tumor spheroid composed of a tumor cell with stromal cell and endothelial cell may better mimic physiological phenomenon compared with the freely distributed system. We quantified the vasculature generated with multicellular tumor spheroid for tortuosity, permeability, and basement membrane coverage, which are known to be different with normal vasculature. This platform consisted of multicellular tumor spheroid surrounded by in-vivo like tumor vasculature could be used in studying the behavior of tumor and personalized medicine.