A novel in vitro 3D cancer model based on modular tissue engineering approach

Abstract

An emerging tool to better recapitulate the complexity of tumor biology in vitro is 3D culture models. Here, we describe a free-floating collagen-based hydrogel system with embedded cancer cells, called microtissues. The microtissues are based on the well-established modular tissue engineering method. They mimic the natural development of the tumor microenvironment, with features such as hypoxia and treatment resistance. To demonstrate the utility of microtissues as a 3D tumor model system, triple negative breast cancer cells were cultured using this method and were shown to maintain cell viability and proliferation with minimal cell death, along with mimicking natural emergence of tumor properties such as, a hypoxic core. Furthermore, by screening the model with commonly used anti-breast cancer chemotherapeutics, we observed drug resistance to concentrations which are largely in accordance with the used doses in the clinics. Therefore, our model offers the opportunity to naturally reproduce fundamental features of a tumor in vitro, leading to emergence of a similar cell reprogramming which is responsible for clinical drug resistance.