Fig. 1.

Novel 3D co-culture system preserves physiologically relevant state and recapitulates chemoresistance in PDAC. A) Schematic description of the 3D model system. Briefly, both tumor and fibroblast cell were derived from same mouse host. Both cell types were brought to single cell level before being encapsulated into Matrigel and type-I collagen mixture to ensure accurate seeding ratio. B) Co-cultured cells maintain physiologically relevant morphologies and molecular markers. Left panel: representative H&E staining of 4-day co-culture. Right panel: representative epithelial tumor marker cytokeratin 19(green), fibroblast marker alpha smooth cell actin (red) and nuclear (DAPI, blue) staining of a 4-day co-culture sample. C, D) 3D co-culture model boosts tumor organoid growth and chemoresistance. C) Left panel: representative phase contrast images of 4-day organoid cultures in different culture conditions. Right panel: quantitative analysis of relative organoid size in each corresponding culture conditions. D) Left panel: representative phase contrast images of 4-day plus 2-day gemcitabine (500 nM) treated organoid cultures in different culture conditions. Right panel: quantitative analysis of relative organoid size in each corresponding culture conditions. For B&C, One-Way ANOVA with Dunnett’s multiple comparison test was performed. *p < 0.05, **p < 0.01, ****p < 0.0001. Error bars represent standard deviation. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)