A Human-Relevant Ex Vivo IBD Model for Therapeutic Development and Preclinical Testing

Improving Translation in Crohn's Disease and Ulcerative Colitis with ex vivo models

Inflammatory bowel disease (IBD), a collective term for Crohn’s disease and ulcerative colitis (UC), is often described as the chronic inflammation of the gut. However, this description does not fully capture the complexity of the condition, nor the challenge it creates for pre-clinical IBD discovery.

To help address this translational challenge, RoukenBio has developed a human-relevant ex vivo IBD model using patient-derived intestinal tissue to support therapeutic testing for Crohn’s disease and ulcerative colitis. By preserving key epithelial, immune and stromal compartments, the model enables drug developers to evaluate therapeutic candidates in a more clinically relevant setting.

In this blog, we explore why advanced IBD models are increasingly important for therapeutic development, how ex vivo approaches can help bridge the translational gap, and why this work has personal significance for RoukenBio Study Manager, Caitlin Dickson, who lives with Crohn’s disease.

Why Advanced IBD Models Are Essential for Therapeutic Development

IBD is not driven by a single pathway. It behaves more like a systems disease, emerging from complex interactions between genetics, the intestinal microbiome, the immune system and environmental factors. This makes it difficult to identify effective treatments that account for the full complexity of the disease.

Multiple preclinical IBD models have been developed to investigate the mechanisms underlying Crohn’s disease and ulcerative colitis. However, models that capture only one axis of disease biology may miss the features that ultimately determine therapeutic efficacy.

For example, a simple in vitro immune-cell assay may demonstrate cytokine suppression but miss epithelial dysfunction, stromal interactions or the important differences between inflamed ileum and rectum. Similarly, an epithelial model may show barrier repair potential but fail to capture the contribution of immune-driven inflammation.

This is why human-relevant IBD models are increasingly critical for successful drug discovery, candidate selection and translational research.

RoukenBio’s Ex Vivo Human IBD Model for Drug Discovery and Therapeutic Testing

RoukenBio’s ex vivo IBD model has been developed to support therapeutic development in a more comprehensive human tissue environment. Starting with biopsy material from patients with Crohn’s disease, ulcerative colitis, or unaffected colon, tissue explants can be cultured to assess therapeutic candidates in a physiologically relevant microenvironment.

This model enables developers to investigate drug response at the site of disease, helping generate more translationally relevant data earlier in the therapeutic development process.

What is an Ex Vivo IBD Model and Why Does It Matter for Drug Discovery?

An ex vivo IBD model is a preclinical research platform that uses patient-derived intestinal tissue to evaluate therapeutic candidates for Crohn’s disease and ulcerative colitis. Unlike simplified in vitro assays or animal models, ex vivo IBD models preserve native tissue architecture, immune cell populations and disease-specific inflammatory responses, providing a more clinically relevant approach to translational drug discovery and therapeutic testing.

Ex vivo IBD models use living tissue derived directly from IBD cultured outside the body to preserve cellular heterogeneity and the local immune microenvironment.

Key Applications of RoukenBio’s Ex Vivo IBD Model

RoukenBio’s ex vivo IBD model can support:

• Mechanism of action studies
• Target validation
• Therapeutic candidate screening
• Cytokine profiling
• Comparative donor response studies
• Translational immunology research

By performing multiplex cytokine analysis of culture supernatants, changes in response can be evaluated in the presence of a therapeutic candidate. 

Immunohistochemistry and immunofluorescent staining can also be used to assess tissue structure and determine whether epithelial barrier repair may be part of the drug’s mechanism of action.

Key advantages of this approach include preservation of human-relevant immune responses, native tissue architecture, patient-specific disease phenotypes, direct ex vivo pharmacological testing and reduced reliance on animal models.

A Personal Perspective on IBD Drug Discovery and Development

While the scientific challenges of IBD are considerable, the impact on patients is equally significant.

“The number of patients being diagnosed with an IBD condition is increasing significantly globally, furthering the demand for effective treatments,” said Caitlin Dickson, Study Manager at RoukenBio.

IBD commonly begins in adolescence or early adulthood, and patients can experience long delays before receiving an accurate diagnosis and appropriate treatment. Caitlin was originally diagnosed with ulcerative colitis in 2017, despite having a family history of Crohn’s disease. It was not until she developed more Crohn’s-specific symptoms, including fistulas, that she received the correct diagnosis and appropriate treatment.

“During a flare-up, Crohn’s can have a really big impact on my day-to-day life that people don’t always see or understand. Fatigue and brain fog are a big part of my symptoms that people don’t expect. Some days, it’s hard to do basic tasks or concentrate at work because I feel completely drained.”

Why Translation Remains a Major Challenge in IBD Drug Discovery

Treatments for IBD have advanced significantly over recent decades. Caitlin explains that when her father was diagnosed with Crohn’s disease in 1997, treatment options were limited to corticosteroids, aminosalicylates and immunosuppressants such as methotrexate. When those treatments failed, surgery was often the next step.

By the time Caitlin was diagnosed in 2017, biologic therapies targeting TNFα, such as adalimumab, and IL-12/23 inhibitors had become important treatment options. However, her experience also highlights one of the ongoing challenges in IBD therapeutic development: treatment response is not always durable.

“However, this only lasted 5 years as my body started to develop auto-antibodies to the drug which made it less effective, and eventually I went into another flare-up. I was then moved onto ustekinumab, targeting IL-12 and IL-23, and fortunately, this has helped me get back into remission.”

Despite advances in biologics and targeted therapies, many IBD programmes continue to face translational challenges due to incomplete understanding of target biology, heterogeneous clinical populations and the limitations of preclinical models that do not fully represent the clinical setting.

Supporting More Translational IBD Therapeutic Development

IBD remains an area of high unmet need. More therapeutic classes are reaching the clinic, treatment options are becoming more diverse, and surgery rates are improving, but patient response remains variable and the underlying disease biology remains difficult to model.

“As a Crohn’s patient, I am happy to currently be in remission, but it is a continuing concern that the treatments working for me now may not be a viable option in a few years’ time,” Caitlin said.

“This is why I am excited by the work we are currently doing at RoukenBio to create a comprehensive model of IBD for therapeutic development. By better capturing disease complexity, we aim to help the development of therapies that offer more consistent, long-term benefit for patients with IBD conditions like myself.”