Human Colon-on-a-Chip Enables Continuous In Vitro Analysis of Colon Mucus Layer Accumulation and Physiology

Abstract

An in vitro method is described for studying colonic mucus physiology by integrating primary human colonic epithelial cells in a microfluidic organ-on-a-chip device. The Colon Chip produces a mucus layer with thickness and bilayered microstructure similar to the human colon. CONCLUSIONS: This study shows the production of colonic mucus with a physiologically relevant bilayer structure in vitro, which can be analyzed in real time noninvasively. The Colon Chip may offer a new preclinical tool to analyze the role of mucus in human intestinal homeostasis as well as diseases, such as ulcerative colitis and cancer.

Research in a time of enteroids and organoids: how the human gut model has transformed the study of enteric bacterial pathogens

“…Platforms should also provide access for on-demand sampling of secreted materials. The microfluidic Intestine-Chip seeded with enteroids from the small intestine [121][122][123][124] or colon 125 offers integrated manipulation of mechanical stretch, anaerobic compartmentalization, and endothelial interfacing. Silk scaffolding provides a highly permeable support network for enteroid monolayer communications with lamina propria.…”

Using Microfluidics to Model Mucus

“…Johansson et al 5 previously reported the necessity of bacterial colonization in vivo in mice to form a mucus bilayer. In contrast, Sontheimer-Phelps et al 2 have reported the establishment of an inner mucus layer sans bacterial interaction in their colon-on-a-chip in vitro model. Further investigations will likely shed light on these paradoxes and establish organ-on-a-chip microfluidic platforms as models for studying mucus production.…”

“…Previously, the generation of a physiologically functional mucus bilayer in vitro had not been realized. Sontheimer-Phelps et al 2 have reported successful in vitro generation of a mucus bilayer using human organoid-derived colonic epithelial cells cultured using an organ-on-a-chip microfluidic device. They show that dynamic flow conditions result in a polarized, confluent colonic epithelial layer that maintained barrier function in vitro.…”

Human Microphysiological Models of Intestinal Tissue and Gut Microbiome

“…In response to prostaglandin E2 the mucus layer underwent volume expansive. This model was responsive to prostaglandin in a Na-K-Cl cotransporter 1 dependent manner (Sontheimer-Phelps et al, 2020). There currently is not an organ chip model of the esophagus, although esophageal organoids have been developed from human pluripotent stem cells.…”