Application of Intestinal Organoids for Studying Inflammatory Bowel Diseases (IBD)

Studying Inflammatory Bowel Disease (IBD)

Inflammatory bowel diseases (IBD) refers to chronic inflammation of the digestive tract such as Crohn’s Disease (CD) and Ulcerative Colitis (UC). Studying IBD can be challenging due to the lack of human models that accurately mimic disease development and progression[Figure 1].

 

Figure 1: The study of gastroenterology can be difficult due to the lack of human models. Organoids derived from stem cells help bridge the gap in studying acute and chronic inflammatory diseases of the intestine.


Most of our knowledge about IBD development has been obtained using mouse models. Although in vivo animal models have some advantages, the obtained results do not necessarily translate to humans. Organoids derived from human stem cells can bridge the gap in studying acute and chronic inflammatory diseases of the intestine. Apart from being less expensive and easier to manipulate, organoids can be generated from patient tissue, so they can be used to develop personalized therapies.

Intestinal Organoids

Intestinal organoids can be developed from stem cells, either by culture of adult intestinal or differentiation of pluripotent stem cells2. This application is promising, as over 200 genetic risk loci have been found to be related to IBD, and intestinal organoids have been increasingly used to identify the role of these genes in disease development and progression3. Intestinal organoids are also becoming more complex with multiple cell types and stroma and have been successfully used to understand the mechanistic action of IBD before the onset of inflammation.

LiveBox 1 for Culturing Intestinal Organoids

The commercially available LiveBox 1 system facilitates the culture of intestinal organoids over a long period of time and is a useful tool to study GI tract inflammatory disorders.  The system is designed for inter-connected dynamic cell cultures and uses perfusion to deliver oxygen and nutrients to cultured organoids. The chamber is transparent with a removable cover to allow live cell imaging, and the glass bottom culture well allows for terminal imaging and recovery of cells for downstream analyses. The culture of normal and patient derived organoids using LiveBox1 has the possibility to speed up the development of efficacious new therapies.

References:

  1. Kiesler P, Fuss IJ, Strober W. Experimental models of inflammatory bowel diseases. Cellular and molecular gastroenterology and hepatology. 2015 Mar 1;1(2):154-70.
  2. Schulte L, Hohwieler M, Mueller M, Klaus J. Intestinal organoids as a novel complementary model to dissect inflammatory bowel disease. Stem cells international. 2019 Mar 19;2019.
  3. Aden K, Tran F, Ito G, Sheibani-Tezerji R, Lipinski S, Kuiper JW, Tschurtschenthaler M, Saveljeva S, Bhattacharyya J, Häsler R, Bartsch K. ATG16L1 orchestrates interleukin-22 signaling in the intestinal epithelium via cGAS–STING. Journal of Experimental Medicine. 2018 Nov 5;215(11):2868-86.