Dataset Information

Intestinal Organoids as a Novel Complementary Model to Dissect Inflammatory Bowel Disease.

ABSTRACT: Inflammatory bowel diseases (IBDs) include colitis ulcerosa and Crohn's disease, besides the rare microscopic colitis. Both diseases show a long-lasting, relapsing-remitting, or even chronic active course with tremendous impact on quality of life. IBDs frequently cause disability, surgical interventions, and high costs; as in other autoimmune diseases, their prevalent occurrence at an early phase of life raises the burden on health care systems. Unfortunately, our understanding of the pathogenesis is still incomplete and treatment therefore largely focuses on suppressing the resulting excessive inflammation. One obstacle for deciphering the causative processes is the scarcity of models that parallel the development of the disease, since intestinal inflammation is mostly induced artificially; moreover, the intestinal epithelium, which strongly contributes to IBD pathogenesis, is difficult to assess. Recently, the development of intestinal epithelial organoids has overcome many of those problems. Here, we give an overview on the current understanding of the pathogenesis of IBDs with reference to the limitations of previous well-established experimental models. We highlight the advantages and detriments of recent organoid-based experimental setups within the IBD field and suggest possible future applications.

SUBMITTER: Schulte L

PROVIDER: S-EPMC6444246 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Intestinal Organoids as a Novel Complementary Model to Dissect Inflammatory Bowel Disease.

Schulte L L Hohwieler M M Müller M M Klaus J J

Stem cells international 20190319

Inflammatory bowel diseases (IBDs) include colitis ulcerosa and Crohn's disease, besides the rare microscopic colitis. Both diseases show a long-lasting, relapsing-remitting, or even chronic active course with tremendous impact on quality of life. IBDs frequently cause disability, surgical interventions, and high costs; as in other autoimmune diseases, their prevalent occurrence at an early phase of life raises the burden on health care systems. Unfortunately, our understanding of the pathogenes ...[more]

PMID: 31015842

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Project description: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 12-days 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.

Dataset Information

Intestinal Organoids as a Novel Complementary Model to Dissect Inflammatory Bowel Disease.

Publications

Intestinal Organoids as a Novel Complementary Model to Dissect Inflammatory Bowel Disease.

Similar Datasets

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