Monitoring small molecules from a colon cancer spheroid model in 3D using MALDI MSI

Organoids and spheroids are attractive 3D cell culture models because they mimic specific in vivo physiological conditions, can be developed from human cells, and contribute towards animal-free research. Their analysis brings light on cell-cell and cell-microenvironment molecular composition and interactions, which creates opportunities in cancer research and drug screening. However, 3D molecular characterization is required for a complete understanding of the molecular composition and chemical changes of the entire system.

Our workflow enables studying cell-cell interactions, invasive cell migration, tumor progression, and other spatially relevant interactions within 3D cell culture models which could be monitored in 3D using MALDI MSI. We analyzed a colon cancer-fibroblast co-culture spheroid model developed by Prof. Rüdiger Rudolf and team, and were able to distinguish between cell type specific small molecules in an unbiased manner and high throughput. Therefore, our 3D technology could enable the identification of desirable markers for studying biological mechanisms typical to each cell type, which could lay the grounds for developing 3D-MSI based drug screenings.