Modeling Endothelialized Hepatic Tumor Microtissues for Drug Screening

Area of Science:

• Biomedical Engineering
• Oncology
• Drug Discovery

Background:

• Traditional 2D cancer models lack the complex microenvironments crucial for understanding tumor behavior.
• 3D scaffold-based models offer biomimetic extracellular matrix and stromal components, including vascularization.
• Hepatic tumor microenvironments are complex and require advanced models for accurate study.

Purpose of the Study:

• To develop a 3D endothelialized hepatic tumor microtissue model.
• To utilize poly(lactic-co-glycolic acid)-based porous microspheres (PLGA PMs) for model construction.
• To evaluate the model's utility in drug screening applications.

Main Methods:

• Coculturing human hepatocellular carcinoma cells and human umbilical vein endothelial cells within PLGA PMs.
• Creating multicellular aggregates within the porous microspheres to form a 3D microtissue.
• Testing the response of cells within the 3D model to anticancer drugs like doxorubicin and cisplatin.
• Investigating the coculture of additional cell types, including fibroblasts (L929) and HepG2 cells.

Main Results:

• The developed 3D model successfully integrated hepatocellular carcinoma cells and endothelial cells within PLGA PMs.
• Cells cultured in the 3D PLGA PMs exhibited significantly higher half-maximal inhibitory concentrations (IC50) for doxorubicin and cisplatin compared to 2D cultures.
• The feasibility of incorporating other cell types, such as fibroblasts and HepG2 cells, was demonstrated.
• The 3D model effectively mimicked aspects of the in vivo tumor microenvironment.

Conclusions:

• Engineered 3D hepatic tumor microtissue models using PLGA PM-based multicellular aggregates are effective for mimicking tumor microenvironments.
• These 3D models provide a more physiologically relevant platform for evaluating drug efficacy compared to traditional 2D methods.
• The developed model holds significant promise for advancing drug screening applications in oncology.