FIG. 8.

Gut-on-a-chip systems for modeling of GI diseases. (a), (b), and (c) The simulation of IBD-related scenarios, and (d) the simulation of colorectal cancer (CRC). (a) (Left) Sketch of various cells interacting in the investigated gut chip: LPS: lipopolysaccharide; (middle and right) the simultaneous exposure to LPS and PBMCs induces epithelial cells to secrete a mixture of cytokines. Images (top-view) demonstrate that the treatment of the epithelium with a particular combination of cytokines causes physical injury. Adapted with permission from Kim et al., Proc. Natl. Acad. Sci. U. S. A. 113(1), E7 (2016).⁹⁴ (b) The decrease in epithelium confluency (DAPI-stained: red) upon the addition of IFN-γ seen across the gut chip microchannel (top-view). Adapted with permission from Apostolou et al., Cell. Mol. Gastroenterol. Hepatol. 12(5), 1719 (2021). Copyright 2021 Elsevier.¹¹⁰ (c) Subjecting the epithelium to a cytokine cocktail, IL-1β, TNF-α, and IFN-γ, for a prolonged duration (11 days) causes the invasion of the epithelium to the neighboring ECM gel (side-view). Adapted with permission from Beaurivage et al., Int. J. Mol. Sci. 20(22), 5661 (2019). Copyright 2019 Authors, licensed under a Creative Commons Attribution (CC BY) license.¹²⁰ (d) The invasion of tumor cells HT29 and HCT116 from the top channel (lumen) into the bottom channel (vascular) across the epithelial and endothelial cells (side-view). Adapted with permission from Strelez et al., iScience, 24(5), 102509 (2021). Copyright 2021 Elsevier.¹²¹