Inflammatory Bowel Disease

Inflammatory bowel disease (IBD), which includes Crohn’s disease and ulcerative colitis, is characterized by intestinal inflammation and disruption of the relationship between the host mucosal epithelium and the intestinal microbial environment. While substantial research has characterized epithelial dysfunction in IBD, and how this instigates an uncontrolled immune response to host tissues, recent evidence has pointed to endothelial dysfunction as an important but incompletely understood component of IBD pathogenesis. The mechanisms underlying endothelial dysfunction in IBD are poorly understood, but studies in other chronic inflammatory diseases states have yielded valuable insight into how this inflammation disrupts end-organ oxygen delivery.  In turn, this causes mitochondrial dysfunction, which compromises the bioenergetic health of an organ and limits the regenerative capacity of injured tissues; this process is amplified in children who have higher metabolic demands compared to adults.

Mucosal healing is the preferred treatment target for patients with IBD, as when this happens, patients have improved outcomes, including decreased risk of surgery

surgery and lower relapse rates. Current treatment strategies involve the use of anti-inflammatory treatments including anti-tumor necrosis factor (anti-TNF) therapy (i.e. infliximab, adalimumab and certolizumab), however, these therapies are given either orally (PO) or intravenously (IV) resulting in their systemic distribution with only a fraction of the dose ever reaching the target diseased mucosa.  Over the years, interventional radiology has been developing minimally invasive image-guided approaches to deliver therapies directly into target tissues via their blood vessels.  This approach ensures maximal tissue concentration of therapy, thereby increasing its efficiency while minimizing systemic toxicity and side effects. For the bowel, interventional radiologists are able to directly access the mesenteric blood supply – either the superior mesenteric artery (SMA) or inferior mesenteric artery (IMA) through endovascular techniques.  Our research has been using these techniques in patients to optimize delivery of therapy as well as developing in the laboratory small animal models of IBD and locoregional techniques to administer MSC and MSC-EVs directly to their inflamed bowel.  Inflammatory bowel disease (IBD), which includes Crohn’s disease and ulcerative colitis, is characterized by intestinal inflammation and disruption of the relationship between the host mucosal epithelium and the intestinal microbial environment. While substantial research has characterized epithelial dysfunction in IBD, and how this instigates an uncontrolled immune response to host tissues, recent evidence has pointed to endothelial dysfunction as an important but incompletely understood component of IBD pathogenesis. The mechanisms underlying endothelial dysfunction in IBD are poorly understood, but studies in other chronic inflammatory diseases states have yielded valuable insight into how this inflammation disrupts end-organ oxygen delivery.  In turn, this causes mitochondrial dysfunction, which compromises the bioenergetic health of an organ and limits the regenerative capacity of injured tissues; this process is amplified in children who have higher metabolic demands compared to adults

Mucosal healing is the preferred treatment target for patients with IBD, as when this happens, patients have improved outcomes, including decreased risk of surgery and lower relapse rates. Current treatment strategies involve the use of anti-inflammatory treatments including anti-tumor necrosis factor (anti-TNF) therapy (i.e. infliximab, adalimumab and certolizumab), however, these therapies are given either orally (PO) or intravenously (IV) resulting in their systemic distribution with only a fraction of the dose ever reaching the target diseased mucosa.  Over the years, interventional radiology has been developing minimally invasive image-guided approaches to deliver therapies directly into target tissues via their blood vessels.  This approach ensures maximal tissue concentration of therapy, thereby increasing its efficiency while minimizing systemic toxicity and side effects. For the bowel, interventional radiologists are able to directly access the mesenteric blood supply – either the superior mesenteric artery (SMA) or inferior mesenteric artery (IMA) through endovascular techniques.  Our research has been using these techniques in patients to optimize delivery of therapy as well as developing in the laboratory small animal models of IBD and locoregional techniques to administer MSC and MSC-EVs directly to their inflamed bowel.