A 3D Collagen-Based In Vitro Cancer Model Created Through Modular Tissue Engineering

Area of Science:

• Biomedical Engineering
• Cancer Biology
• 3D Cell Culture

Background:

• 3D culture models are emerging tools for simulating tumor biology in vitro.
• Existing models face challenges in technical complexity and reproducing critical tumor traits.
• Modular tissue engineering, successful in healthy tissue transplantation, is adapted for cancer research.

Purpose of the Study:

• To adapt modular tissue engineering for fabricating cancer microtissues.
• To assess the effectiveness of these microtissues as a tumor model.
• To evaluate their ability to capture essential cancer biology features and drug response.

Main Methods:

• Two triple-negative breast cancer cell lines (HCC1806, MDA-MB-231) were cultured in microtissues.
• Assessed microtissues for viability, cell death, hypoxia, and chemotherapy response.
• Used flow cytometry to analyze cancer stem cell (CSC) phenotype (CD44+/CD24-) across different 3D models and 2D cultures.

Main Results:

• Microtissues demonstrated sustained viability, minimal cell death, and spontaneous development of tumor properties like hypoxia.
• Flow cytometry revealed cell-line-dependent regulation of the CD44+/CD24- CSC phenotype in the 3D microenvironment.
• The model exhibited drug resistance to standard chemotherapeutics at clinically relevant concentrations.

Conclusions:

• The developed microtissue model spontaneously reproduces fundamental in vitro tumor features.
• It effectively captures cellular heterogeneity and reprogramming contributing to clinical drug resistance.
• This model serves as a valuable tool for studying complex cancer biology and treatment response.