Ultrastructural Study of Microphysiological Systems of the Tumor Microenvironment

Area of Science:

• Biomedical Engineering
• Cancer Research
• Microscopy

Background:

• Ultrastructural studies are crucial for understanding disease pathology and diagnosis.
• Cancer-on-a-chip models offer promise for studying tumors but lack ultrastructural analysis due to complex sample preparation.
• Miniaturized models exacerbate sample preparation challenges for electron microscopy.

Purpose of the Study:

• To investigate the ultrastructural features of microphysiological systems (MPS) modeling the tumor microenvironment.
• To develop and validate a sample preparation technique for observing 3D multicellular tumor structures in cancer-on-a-chip models using advanced electron microscopy.

Main Methods:

• Utilized dual-beam focused ion beam scanning electron microscopy (FIB-SEM) and transmission electron microscopy (TEM).
• Devised a novel sample preparation technique for hydrogel-based cancer-on-a-chip models.
• Analyzed two distinct MPS examples from laboratory settings.

Main Results:

• Achieved high-resolution visualization of both external and internal structures of 3D multicellular tumor spheroids.
• Detailed observation of cell-matrix interactions, cell-cell junctions, and spheroid-spheroid contacts.
• Visualized matrix deposition and extracellular vesicle-mediated intercellular communication within the tumor models.

Conclusions:

• Demonstrated the feasibility of applying advanced electron microscopy techniques to miniaturized cancer models.
• Opened new avenues for ultrastructural analysis in cancer-on-a-chip systems.
• Highlighted the potential of these models for uncovering tumor processes and identifying novel therapeutic targets.