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Intestinal Stricture Research Services

Intestinal stricture is one of the most difficult to treat and most common complications of Crohn's disease (CD). Approximately 70% of CD patients develop fibrotic strictures 10 years after the diagnosis of CD. There is growing evidence implying that the pathogenesis of CD involves the intricate interplay of factors. Although anti-inflammatory therapies can alleviate inflammation and improve histological healing, they fall far short of a resolution for strictures. There are no reliable methods for accurately evaluating intestinal fibrosis. Currently, the progress on intestinal strictures has been fueled by the advent of novel techniques, such as single-cell sequencing, multi-omics, and artificial intelligence.

Fig. 1. Overview of the main pathophysiological mechanisms behind fibro-stenosing CD. (Solitano, et al., 2023)

Customized Studies for Intestinal Stricture

With expertise and extensive experience in the field of Crohn's disease, Ace Therapeutics is at the forefront of preclinical intestinal stricture research. We offer customized services to help clients explore the mechanisms of initiation and propagation of intestinal strictures and develop novel diagnostic techniques and therapies for intestinal strictures.

We are very experienced in the study of intestinal strictures characterized by both:

• Inflammatory strictures are caused by the inflammation of the digestive tract that accompanies a Crohn's flare-up.
• Fibrotic strictures are the result of scar tissue building up in the bowel due to long periods of inflammation.

Animal Models of Intestinal Fibrosis

A frequent complication of Crohn's disease is fibrosis, which leads to strictures and stenoses that narrow the gut lumen and cause obstruction. Ace Therapeutics provides relevant and tractable models of intestinal fibrosis to help clients uncover novel mechanisms of fibrostenotic disease in human CD.

• The SAMP1/Yit mouse model of intestinal fibrosis
• The TNF^ΔARE mouse model of intestinal fibrosis
• TNBS-induced intestinal fibrosis
• DSS-induced colitis
• IL-10-/- models
• TGF-β1 overexpression models
• MCP-1 overexpression models

Assessment of Intestinal Fibrosis in Animals

We perform several clinically relevant outcome assays in these models to enhance understanding and drug development for intestinal fibrosis, including features of structural fibrosis, histologic fibrosis, and gene expression. These include the use of a new luminal casting technique, traditional histologic outcomes, use of second harmonic imaging, and quantitative PCR.

• Measurements of casted ileum for determination of presence of stricture and ileal narrowing
• Determination of luminal area
• Histological examination of intestinal fibrosis
• Wall width measurements
• Collagen content measurement in the terminal ileum
• Fibrosis scoring
• Pro-inflammatory and profibrotic gene expression in the terminal ileum
• Profiling the progression to ileal fibrosis in animals
• Using imaging technique to accurately quantify the amount of fibrosis in a stricture

Whether you need mechanistic studies or therapies development for intestinal fibrosis, Ace Therapeutics provides technical support throughout the process. Our multidisciplinary teams aim to deliver fast cycle times, with close communication and determination to ensure the success of your drug discovery project for intestinal fibrosis. Contact us today for more!