Inflammatory Bowel Disease Model

With a strong focus on immuno-oncology applications, we provide translational in vivo efficacy studies, PK/PD, toxicity studies, and in vitro pharmacology support.

Inflammatory bowel disease (IBD) refers to chronic inflammatory disease of the colon or gastrointestinal tract, including ulcerative colitis (UC) and Crohn’s disease (CD). Clinical symptoms of IBD include diarrhea, abdominal pain, intestinal bleeding/hematochezia, fever, and weight loss. The pathogenesis of IBD is not clear, however studies have shown that various factors such as genetic, immune system, external environment and intestinal microorganisms are associated with the occurrence of IBD.

A variety of preclinical mouse models are currently used to study IBD. Depending on the specific use, different induction methods can yield disease models. The mouse enteritis model conferred by dextran sulfate sodium (DSS) is the most widely used chemically-induced mouse IBD model. Acute ulcerative enteritis or chronic colitis is induced in mice by dissolving DSS in drinking water, resulting in loss of intestinal epithelial cells, cytokine release by non-specific immune cells, and disruption in the integrity of the mucosal barrier. IBD-induced mouse models experience significant weight loss, loose stools, hematochezia, and granulocyte infiltration, altogether suggesting that pathological features and clinical symptoms are similar to those seen in human ulcerative colitis.

Biocytogen generated a stable IBD-induced model using DSS in wild-type C57BL/6 mice, which can be used for preclinical studies and pharmacodynamic evaluation of inflammatory enteritis.

Establishment of IBD Mouse Model

Experimental Animals:C57BL/6, 7-8 weeks old, female

Modeling reagent:DSS

Modeling method:dosing with DSS in drinking water for 7 consecutive days

Induction of IBD in Mice

Wild-type C57BL/6 mice were provided drinking water containing DSS for 7 consecutive days for IBD induction. (A-C) Change in mouse body weight for each experimental group (G1-G4). (D) Disease activity index (DAI) score for each experimental group (G1-G4). Body weight of DSS-treated mice (G2) decreased compared to control vehicle-treated mice (G1), furthermore, the DAI score for DSS-treated mice indicated increased disease severity. Body weight and DAI scores for IBD mice treated with different doses of cyclosporin A (CsA) did not change significantly. Altogether, this data shows that IBD was successfully established in C57BL/6 mice by DSS, and CsA relieved clinical symptoms of IBD in a dose-dependent manner.

Gross Sampling and Colon Evaluation

Comparison of colons in C57BL/6 mice with DSS-induced inflammatory bowel disease. (A) Colon length, (B) colon weight to body weight ratio and (C) the ratio of colon weight to colon length were measured for each experimental group (G1-G4). Colon weight and length were significantly abnormal in DSS-induced IBD mice (G2) compared to control vehicle-treated mice (G1). However, colon weight and length improved in CsA-treated mice (G3, G4), suggesting CsA alleviates colonic symptoms in IBD mice.

Pathological Assessment of CsA-Treated IBD Mice

CsA treatment significantly alleviates IBD-like colon lesions in DSS-induced IBD mice. (A) H&E staining of colons and (B) pathological scores were assessed for each experimental group (G1-G4). Compared to control mice (G1), inflammatory cell infiltration was observed in DSS-treated mice (G2) indicative of destroyed intestinal epithelial cells and intestinal mucosal layer. In CsA-treated IBD mcie, colonic symptoms were significantly relieved in a dose-dependent manner.

Altogether, these data suggest that DSS colitis in C57BL/6 mice was established, and cyclosporin A (CsA) could significantly alleviate DSS-induced inflammatory bowel disease colon lesions.

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