Breast Cancer Reconstruction: Design Criteria for a Humanized Microphysiological System

Area of Science:

• Biomedical Engineering
• Cancer Research
• In Vitro Models

Background:

• Regulatory agencies mandate developing humanized microphysiological systems (MPS) as in vitro alternatives to animal models.
• Breast cancer research acknowledges the importance of 3D growth dynamics but faces obstacles in fully adopting humanized MPS.
• Existing models often rely on animal-derived components, limiting their translatability to human physiology.

Purpose of the Study:

• To evaluate the current status of human tissue-derived cells and scaffolds for creating an idealized breast cancer MPS.
• To assess adipose tissue as a source for essential cell types (endothelial, lymphohematopoietic, stromal) in breast cancer models.
• To compare potential MPS scaffolds (adipose, blood, synthetic) against the current gold standard, Matrigel.

Main Methods:

• Bioengineering design principles applied to breast cancer MPS.
• Evaluation of human tissue-derived cells and extracellular matrices as building blocks.
• Comparative analysis of scaffold materials including adipose tissue, blood components, synthetic biomaterials, and Matrigel.

Main Results:

• Adipose tissue is a viable source for key stromal and vascular cells supporting breast cancer epithelial growth.
• Various human-derived biomaterials show potential as scaffolds, offering alternatives to murine-derived Matrigel.
• The study discusses the advantages and limitations of different components for in-process and destructive read-out assays.

Conclusions:

• Human-derived cells, extracellular matrices, and hydrogels are crucial building blocks for advanced breast cancer MPS.
• These humanized MPS models can better reflect patient diversity (ethnicity, pathophysiology, metabolic status).
• The development of humanized MPS aligns with regulatory calls for more predictive, human-relevant models and reduced animal testing.