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Figure 1. An example of pancreatic tumor organoids growing in culture and in vivo. (A) A brightfield microscopy image of organoids growing in structured 3D spheres in Matrigel in vitro. Organoids can be efficiently generated from a wide range of epithelial tissues and, as they are genetically stable over an extended time in culture, are amenable to genetic manipulation. (B) A schematic of how an organoid’s sensitivity to a therapeutic can be presented. Organoid cell viability can be measured in a high-throughput manner by standard assay techniques [e.g., CellTiter-Glo (Promega)] and plotted against drug or ADC concentration. The therapeutic responses of normal, tumor, and metastatic organoids derived from the same patient, organoids from different patients, or genetically modified variant organoids can be readily compared. (C) Two serial sections of a pancreatic tumor developed in vivo following orthotopic implantation of tumor organoid cells. The top panel is an H&E stain, highlighting regions of tumor cells in deep purple. The bottom panel is a Masson’s trichrome stain, which stains collagen blue. These organoid tumors develop a dense stroma composed of connective tissue and fibroblasts when grown orthotopically in vivo, recapitulating key clinical characteristics.