Table 1.

Experimental modeling systems for intercellular interactions.

Model System	Sample	Method Description	Reference
2D cell culture	Cells	Cells grow in a monolayer if adherent or suspended in a culture flask. These cultures are a straightforward, cost-effective, and low-maintenance approach. Within the controlled environment, it is possible to investigate the interactions between different cell lines and observe their behavior and responses to treatments.	[24]
3D cell culture	Cells	Cell growth and interactions occur in 3D space, where cells interact with their surrounding environment and neighboring cells. Two approaches: scaffold-based methods using hydrogels or structural scaffolds and scaffold-free techniques (spheroids).	[24]
Spheroids	Cells	Organoids, also known as multicellular spheroids, are self-assembled structures that mimic the physiological environment and interactions found in vivo. They provide a more physiologically relevant context, allowing the investigation of intercellular interactions and responses within a 3D microenvironment resembling in vivo conditions.	[25]
Organoids	Patient-derived cells and tissues	Primary patient-derived microtissues grown in a 3D extracellular matrix that represents in vivo physiology and genetic diversity, allowing the investigation of intercellular interactions and responses in a patient-specific manner.	[26]
Tissue Slices	Tumor Tissue	Tumor biopsy taken from patients or xenograft models, stained to assess tumor morphology and spatial location of cells.	[27]
Animal models	Tumor Tissue	Compatible with intravital and intercellular imaging/labeling techniques, as well as other genetic systems designed to detect cell–cell interactions upon contact or external stimulation, including UV or fluorescent light.	[28]