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3D bioengineered tissue model of the large intestine to study inflammatory bowel disease.

ABSTRACT: An in vitro model of intestinal epithelium with an immune component was bioengineered to mimic immunologic responses seen in inflammatory bowel disease. While intestinal immune phenomena can be modeled in transwells and 2D culture systems, 3D tissue models improve physiological relevance by providing a 3D substrate which enable migration of macrophages towards the epithelium. An intestinal epithelial layer comprised of non-transformed human colon organoid cells and a subepithelial layer laden with monocyte-derived macrophages was bioengineered to mimic native intestinal mucosa cell organization using spongy biomaterial scaffolds. Confluent monolayers with microvilli, a mucus layer, and infiltration of macrophages to the basal side of the epithelium were observed. Inflammation, induced by E. coli O111:B4 lipopolysaccharide and interferon ? resulted in morphological changes to the epithelium, resulting in ball-like structures, decreased epithelial coverage, and increased migration of macrophages to the epithelium. Analysis of cytokines present in the inflamed tissue model demonstrated significantly upregulated secretion of pro-inflammatory cytokines that are often associated with active inflammatory bowel disease, including CXCL10, IL-1?, IL-6, MCP-2, and MIP-1?. The macrophage layer enhanced epithelial and biochemical responses to inflammatory insult, and this new tissue system may be useful to study and develop potential therapies for inflammatory bowel disease.

SUBMITTER: Roh TT

PROVIDER: S-EPMC6908826 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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3D bioengineered tissue model of the large intestine to study inflammatory bowel disease.

Roh Terrence T TT Chen Ying Y Paul Harry T HT Guo Chengchen C Kaplan David L DL

Biomaterials 20190925

An in vitro model of intestinal epithelium with an immune component was bioengineered to mimic immunologic responses seen in inflammatory bowel disease. While intestinal immune phenomena can be modeled in transwells and 2D culture systems, 3D tissue models improve physiological relevance by providing a 3D substrate which enable migration of macrophages towards the epithelium. An intestinal epithelial layer comprised of non-transformed human colon organoid cells and a subepithelial layer laden wi ...[more]

PMID: 31580968

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Project description:Background and aimsThe objective of this study was to evaluate the risk of colorectal cancer (CRC) in patients taking aminosalicylates (5-ASA) for inflammatory bowel disease (IBD).MethodsThe General Practice Research Database (GPRD) which contains the primary care records of five million people in the UK was used to identify users of mesalazine, balsalazide, olsalazine, or sulfasalazine with a history of IBD. In a nested case control analysis, each incident CRC case with any use of a 5-ASA in the six months before the CRC diagnosis was matched by age, sex, and calendar time to six control patients who were also currently using a 5-ASA. Patients were then classified according to regularity of use. The analysis was controlled for body mass index, IBD duration, history of colorectal polyps, use of non-steroidal anti-inflammatory drugs, paracetamol, aspirin, immunosuppressants, oral and rectal glucocorticoids, prior gastrointestinal hospitalisation, recorded colonoscopy, and number of visits to the general practitioner for IBD symptoms in the 6-24 months before diagnosis.ResultsThe study population included 18 969 patients, of whom 100 had developed CRC during 5-ASA exposure. Most of these cases had a history of ulcerative colitis (76 patients). In the case control analysis, regular users, defined as having six or more 5-ASA prescriptions in the previous 12 months, were found to have a decreased risk of CRC compared with irregular users (crude odds ratio (OR) 0.7 (0.44-1.03); adjusted OR 0.60 (0.38-0.96)). Regular users of sulfasalazine with 6-12 prescriptions before had an adjusted OR of 0.95 (0.22-4.11); with 13-30 prior prescriptions this was 0.41 (0.14-1.20) and with >30 prior prescriptions this was 0.77 (0.37-1.60). For mesalazine users, these values were 1.13 (0.49-2.59), 0.30 (0.11-0.83), and 0.31 (0.11-0.84), respectively.ConclusionThese results show that regular 5-ASA use is associated with some reduction in the risk of CRC developing in ulcerative colitis.

Dataset Information

3D bioengineered tissue model of the large intestine to study inflammatory bowel disease.

Publications

3D bioengineered tissue model of the large intestine to study inflammatory bowel disease.

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