Fig. 2.

Building multi-dimensional organoids that emulate the complexity of the gut. Schematic displays the isogenic cell components derived from the same patient that can be used to build multidimensional organoid-based CRC models. Blood and tumor tissue collected from the same patient (A) can be used as a source of immune cells (B, top) or tumor organoids and tumor-associated stromal cells (B, bottom). Coculture models can then be assembled to preserve the physiologic orientation of tissue (i.e., basolateral side of the tumor epithelium facing stroma and immune cells; see C). Complexity can be further increased with the addition of fecal microbes from the same patient. Although not shown here, components of the enteric nervous system can also be incorporated into the coculture where desired. Such an understanding-by-modeling approach is critical to creating wholesome models for testing drug efficacy or for testing fundamental research hypotheses in the setting of complex cell types.