Epithelial organoid cultures from patients with ulcerative colitis and Crohn's disease: a truly long-term model to study the molecular basis for inflammatory bowel disease?

Noben, Manuel; Verstockt, Bram; Bruyn, Magali de; Hendriks, Nikolai; Assche, Gert Van; Vermeire, Séverine; Verfaillie, Catherine M.; Ferrante, Marc

doi:10.1136/gutjnl-2016-313667

Cited by 37 publications

(29 citation statements)

References 3 publications

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“…Enteroids have also contributed to the understanding of cystic fibrosis caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) using a swelling assay (Dekkers et al, 2013 ). Moreover, enteroids have been used to model colorectal cancer and inflammatory bowel disease including ulcerative colitis and Crohn's disease (Matano et al, 2015 ; Young and Reed, 2016 ; Noben et al, 2017 ). Finally, the potential transplantation of enteroids into patients with intestinal failure (IF), a life-threatening condition, further expanded the possibility of using enteroids to treat patients (Hong et al, 2017 ).…”

Section: Lessons Learned From Studies Of Other Enteropathogensmentioning

confidence: 99%

Organoid and Enteroid Modeling of Salmonella Infection

Yin

Zhou

2018

Front. Cell. Infect. Microbiol.

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Salmonella are Gram-negative rod-shaped facultative anaerobic bacteria that are comprised of over 2,000 serovars. They cause gastroenteritis (salmonellosis) with headache, abdominal pain and diarrhea clinical symptoms. Salmonellosis brings a heavy burden for the public health in both developing and developed countries. Antibiotics are usually effective in treating the infected patients with severe gastroenteritis, although antibiotic resistance is on the rise. Understanding the molecular mechanisms of Salmonella infection is vital to combat the disease. In vitro immortalized 2-D cell lines, ex vivo tissues/organs and several animal models have been successfully utilized to study Salmonella infections. Although these infection models have contributed to uncovering the molecular virulence mechanisms, some intrinsic shortcomings have limited their wider applications. Notably, cell lines only contain a single cell type, which cannot reproduce some of the hallmarks of natural infections. While ex vivo tissues/organs alleviate some of these concerns, they are more difficult to maintain, in particular for long term experiments. In addition, non-human animal models are known to reflect only part of the human disease process. Enteroids and induced intestinal organoids are emerging as effective infection models due to their closeness in mimicking the infected tissues/organs. Induced intestinal organoids are derived from iPSCs and contain mesenchymal cells whereas enteroids are derive from intestinal stem cells and are comprised of epithelial cells only. Both enteroids and induced intestinal organoids mimic the villus and crypt domains comparable to the architectures of the in vivo intestine. We review here that enteroids and induced intestinal organoids are emerging as desired infection models to study bacterial-host interactions of Salmonella.

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Section: Lessons Learned From Studies Of Other Enteropathogensmentioning

confidence: 99%

Organoid and Enteroid Modeling of Salmonella Infection

Yin

Zhou

2018

Front. Cell. Infect. Microbiol.

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“…These genes include LYZ, CLDN18, hZG16, hCLCA1, MUC12, and AQP8, which are involved in antimicrobial, barrier, mucus production or water transport functions. Another study recently confirmed that differential expression of mucus production gene (MUC2) is observed in organoids from IBD patients, and in particular from Crohn's disease patients, compared to controls (Noben et al, 2017). Taken together, such data implies that long-lasting epithelial defects are present in IBD patient epithelium, and may be acquired during the course of the disease thereby contributing to the perpetuation of the pathology.…”

Section: Discussionmentioning

confidence: 71%

“…The epithelium generated by three-dimension cultures of isolated crypts closes on itself, forming a sphere, in which epithelial cells are orientated with their apical side toward the lumen (Sébert et al, 2018). While a number of studies have employed culture organoids from intestinal crypts (Sugimoto et al, 2018;Yip et al, 2018;Ramesh et al, 2019), only very few studies have investigated the possibility to culture organoids from IBD patient-isolated intestinal crypts (Dotti et al, 2017;Noben et al, 2017;Howell et al, 2018). Importantly, they reported transcriptional or methylation differences between organoids from UC or CD patients compared to controls (Dotti et al, 2017;Howell et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Characterization of Human Colon Organoids From Inflammatory Bowel Disease Patients

d'Aldebert

Quaranta

Sébert

et al. 2020

Front. Cell Dev. Biol.

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Inflammatory Bowel Diseases (IBD) are chronic inflammatory disorders, where epithelial defects drive, at least in part, some of the pathology. We reconstituted human intestinal epithelial organ, by using three-dimension culture of human colon organoids. Our aim was to characterize morphological and functional phenotypes of control (non-IBD) organoids, compared to inflamed organoids from IBD patients. The results generated describe the epithelial defects associated with IBD in primary organoid cultures, and evaluate the use of this model for pharmacological testing of anti-inflammatory approaches. Human colonic tissues were obtained from either surgical resections or biopsies, all harvested in non-inflammatory zones. Crypts were isolated from controls (non-IBD) and IBD patients and were cultured up to 12-days. Morphological (size, budding formation, polarization, luminal content), cell composition (proliferation, differentiation, immaturity markers expression), and functional (chemokine and tight junction protein expression) parameters were measured by immunohistochemistry, RT-qPCR or western-blot. The effects of inflammatory cocktail or anti-inflammatory treatments were studied in controls and IBD organoid cultures respectively. Organoid cultures from controls or IBD patients had the same cell composition after 10 to 12days of culture, but IBD organoid cultures showed an inflammatory phenotype with decreased size and budding capacity, increased cell death, luminal debris, and inverted polarization. Tight junction proteins were also significantly decreased in IBD organoid cultures. Inflammatory cytokine cocktail reproduced this inflammatory phenotype in non-IBD organoids. Clinically used treatments (5-ASA, glucocorticoids, anti-TNF) reduced some, but not all parameters. Inflammatory phenotype is associated with IBD epithelium, and can be studied in organoid cultures. This model constitutes a reliable human pre-clinical model to investigate new strategies targeting epithelial repair.

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“…Noben et al 3 addressed that an inflammatory status of the inflamed tissue may not be propagated to organoids cultures, and stimuli are needed for specific studies. Both tumour necrosis factor alpha and interferon gamma have been reported to induce intestinal barrier dysfunction in IBD,4 while the underlying mechanisms remain unclear.…”

mentioning

confidence: 99%