3D spheroid cultures are increasingly used to answer mechanistic questions about tumor growth and serve to screen new therapeutics. Therefore, it is critical that these models are clinically representative. We focus on replicating the desmoplasia seen in many cancers, including pancreatic cancer, using this technique.
Spheroid cultures have evolved to incorporate patient-derived cells, complex co-cultures with immune cells, and physiological structures like vasculature. Additionally, microfluidic technology is employed for high-throughput screening and creating organ-on-a-chip systems. Multi-omic profiling in spheroids is now utilized to gain mechanistic insights.
The described method can be used to create reproducible 3D co-cultured spheroids with a robust ECM free of synthetic matrix materials. The advantage is that the ECM closely replicates clinical tumors without their relevant synthetic matrix interfering with therapeutic screening applications. This model will enable the valuation of ECM response to therapeutics and answer important mechanism questions on the dynamic barrier that the ECM presents in numerous cancers.
We plan to expand this model to include immune cell and macrophage components in addition to expanding the model used to understand ECM as a barrier to therapeutics and diseases outside of cancer such as tuberculosis granulomas.