Creation of a spatially complex mucus bilayer on an in vitro colon model
Year: 2024
Type: article
Abstract: The colonic epithelium is comprised of three-dimensional crypts (3D) lined with mucus secreted by a heterogeneous population of goblet cells. In this study, we report the formation of a long-lived, and self-renewing replica of human 3D crypts with a mucus layer patterned in the X-Y-Z dimensions. Primary colon cells were cultured on a shaped scaffold under an air-liquid interface to yield architecturally accurate crypts with a mucus bilayer (605 ± 180 μm thick) possessing an inner (149 ± 50 μm) and outer (435 ± 111 μm) region. Lectins with distinct carbohydrate-binding preferences demonstrated that the mucus in the intercrypt regions was chemically distinct from that above and within the crypts replicating in vivo chemical patterning. Constitutive mucus secretion ejected beads from crypt lumens in 8-10 days, while agonist-stimulated secretion increased mucus thickness by 17-fold in 8 h. The tissue was long-lived, > 50 days, the longest time assessed. In conclusion, the in vitro mucus replicated key physiology of the human mucus, including the bilayer (Z) structure and intercrypt-crypt (X-Y) zones, constitutive mucus flow, spatially complex chemical attributes, and mucus secretion response to stimulation, with the potential to reveal local and global determinants of mucus function and its breakdown in disease.
Source: Scientific Reports
Institution: University of Washington
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,590
Awards: Development of a microphysiologic system to assay the interaction of the human colonic epithelium on Clostridium difficile, G6161852781, G8108422591, Developing an optimized cell based platform for assays of the gastrointestinal enteroendocrine system, Developing a platform and optimized cell system for enteroendocrine cell-based assays and compound screening, G9000135049
OpenAlex ID: W4400872184