Modeling Endothelialized Hepatic Tumor Microtissues for Drug Screening

Abstract

Compared to various traditional 2D approaches, the scaffold-based 3D tumor models have emerged as an effective strategy to investigate the complex mechanisms behind cancer progression and responses to drug treatments, by providing biomimetic extracellular matrix and stromal-like microenvironments including the vascular elements. Herein, the development of a 3D endothelialized hepatic tumor microtissue model based on the fusion of multicellular aggregates of human hepatocellular carcinoma cells and human umbilical vein endothelial cells cocultured in poly(lactic-co-glycolic acid)-based porous microspheres (PLGA PMs) is reported. In contrast to the conventional 2D culture, the cells within the PLGA PMs exhibit significantly higher half-maximal inhibitory concentration values against anticancer drugs, including doxorubicin and cisplatin. Furthermore, the feasibility of coculturing other cell types, such as fibroblasts (L929) and HepG2 cells, is investigated. Together, the findings emphasize the significance of engineered 3D hepatic tumor microtissue models using PLGA PM-based multicellular aggregates for drug screening applications.