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<https://discovery.ucl.ac.uk/id/eprint/10203094> <http://purl.org/dc/terms/title> "Organoid-based regenerative medicine technologies across regions and developmental stages of the gastrointestinal tract"^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/eprint/10203094> <http://purl.org/ontology/bibo/abstract> "Regenerative medicines have the potential to produce personalised therapies\r\nby combining knowledge of stem cell biology with biomedical engineering. To\r\nrealise this potential in the gastrointestinal (GI) tract, normal development of\r\nthe GI epithelium and its response to injury must be understood. Epithelial\r\norganoids derived from different regions of the GI tract and across\r\ndevelopmental time are a valuable human-specific in vitro system to\r\nunderstand development, homeostasis, and injury, and could be a source of\r\ncells for therapy when combined with an appropriate delivery method.\r\nIn this work, a technique for surgical mucosectomy of the mouse colon was\r\ndeveloped, that successfully left an intact vascularised neuromuscular coat\r\nonto which intestinal organoid-based mucosal grafts could be delivered. The\r\naim was to ‘intestinalise’ the colon for treatment of short bowel syndrome.\r\nWhen this project was forced to close by SARS-CoV-2 pandemic, the\r\ntechnique’s components were feasible but high mortality in live mice\r\nnecessitates further optimisation of the model.\r\nFor the first time, this work describes human foetal and paediatric epithelial\r\ngastric organoids (GOs), including gastric region-specific GOs. GOs were\r\nreliably derived, even from sub-centimetre endoscopic biopsies, were\r\nexponentially expandable and genetically stable in culture, and retained\r\nmemory of their developmental stage and region of derivation. GOs with\r\nreversed cellular polarity were used to model SARS-CoV-2 infection in the\r\ngastric epithelium, demonstrating age-related susceptibility (greatest in late\r\nfoetal and paediatric GOs) associated with induction of interferon stimulated\r\ngenes but minimal expression of interferons. Floating co-culture of fundus,\r\nbody, and antrum GOs in custom mini wells allowed GOs to self-organise into\r\nmulti-region models of the stomach. This model resulted in a broader diversity\r\nof differentiated cell types and greater transcriptional similarity to native tissue,\r\nincreasing the fidelity of the in vitro gastric epithelial model beyond what had\r\nbeen achieved to date."^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/eprint/10203094> <http://purl.org/dc/terms/date> "2025-01-28" .
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