Creation of a spatially complex mucus bilayer on an in vitro colon model.
Air–liquid interface
Colon-on-chip
Crypt
Goblet cell
Microphysiologic system
Mucus
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
22 Jul 2024
22 Jul 2024
Historique:
received:
28
02
2024
accepted:
12
07
2024
medline:
23
7
2024
pubmed:
23
7
2024
entrez:
22
7
2024
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 39039235
doi: 10.1038/s41598-024-67591-9
pii: 10.1038/s41598-024-67591-9
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
16849Subventions
Organisme : NIDDK NIH HHS
ID : DK120606
Pays : United States
Organisme : NIDDK NIH HHS
ID : DK121580
Pays : United States
Informations de copyright
© 2024. The Author(s).
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