Long-term in vitro 3D hydrogel co-culture model of inflammatory bowel disease

DOSH, Rasha H, JORDAN-MAHY, Nicola, SAMMON, Christopher and LE MAITRE, Christine L (2019). Long-term in vitro 3D hydrogel co-culture model of inflammatory bowel disease. Scientific reports, 9 (1), p. 1812.

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Open Access URL: https://www.nature.com/articles/s41598-019-38524-8 (Published version)
Link to published version:: https://doi.org/10.1038/s41598-019-38524-8

Abstract

The in vitro study of the pathogenesis of inflammatory bowel disease (IBD) requires a cell model which closely reflects the characteristics of the in vivo intestinal epithelium. This study aimed to investigate the application of L-pNIPAM hydrogel as a scaffold to develop a long-term 3D co-culture model of Caco-2 and HT29-MTX cells under conditions analogous to inflammation, to determine its potential use in studying IBD. Monocultures and co-cultures were layered on L-pNIPAM hydrogel scaffolds and maintained under dynamic culture conditions for up to 12 weeks. Treatments with IL-1β, TNFα, and hypoxia for 1 week were used to create an inflammatory environment. Following prolonged culture, the metabolic activity of Caco-2 monoculture and 90% Caco-2/10% HT29-MTX co-cultures on L-pNIPAM hydrogels were increased, and finger-like structures, similar in appearance to villi were observed. Following treatment with IL-1β, TNFα and hypoxia, ALP and ZO-1 were decreased, MUC2 increased, and MUC5AC remained unchanged. ADAMTS1 was increased in response to hypoxia. Caspase 3 expression was increased in response to TNFα and hypoxic conditions. In conclusion, L-pNIPAM hydrogel supported long-term co-culture within a 3D model. Furthermore, stimulation with factors seen during inflammation recapitulated features seen during IBD.

Item Type: Article
Identification Number: https://doi.org/10.1038/s41598-019-38524-8
SWORD Depositor: Symplectic Elements
Depositing User: Symplectic Elements
Date Deposited: 26 Feb 2019 16:29
Last Modified: 28 Feb 2019 13:15
URI: http://shura.shu.ac.uk/id/eprint/24103

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