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Short Bowel Syndrome (SBS) is a medical disorder caused by a lack of a fully functional small intestine. Whether caused as a birth defect or because part of the small intestine was removed during surgery, SBS is a rare disorder, affecting approximately 13 000 people in the European Union. If left untreated, the condition can prevent the gut from performing its nutritional function.
Unfortunately, there is no cure for SBS, and current treatment options have low survival rates and can cause serious side-effects – especially for children. That is why researchers with the EU-funded INTENS project are committed to developing a better solution.
“Our aim is to deliver a functional small bowel that could be used to treat patients with SBS,” says Paolo De Coppi, National Institute for Health Research professor of paediatric surgery at the UCL Great Ormond Street Institute of Child Health and INTENS project coordinator.
Surpassing all expectations
Today, treating SBS requires long-term parenteral nutrition (nutrition provided through the vein) or an organ transplant. While the former does not offer a definitive cure, the latter is associated with a shortage of organs. As a result, both treatment approaches are of a limited effect.
To overcome this challenge, the INTENS project focused on developing a strategy for autologous tissue engineering – or the process of treating an individual using their own cells or tissues. “This approach would allow us to overcome the shortage of organs and avoid the need for the risky practice of suppressing the patient’s immune response,” remarks De Coppi. “The results we have achieved so far have surpassed all expectations.”
An example of this strategy can be seen in the project’s construction of autologous jejunal mucosal grafts. “In other words, we used biomaterials from SBS paediatric patients to engineer living tissue of the lining found in the small intestine that could, in theory, be surgically transplanted,” explains De Coppi.
Researchers also discovered the similarities between the small intestine and colon scaffolds (i.e., the engineered materials used to form new functional tissues). According to De Coppi, this indicates that they could be interchangeably used as platforms for intestinal engineering. “This opens the door to using the residual colon as scaffolding in children who have lost their entire small bowel,” he says.
To support this finding, De Coppi and his team transplanted the colon scaffolds in vivo, demonstrating that they can survive to form short-term functional structures. “These findings provide proof-of-concept data for engineering patient-specific jejunal grafts for children with intestinal failure, ultimately restoring their nutritional autonomy,” adds De Coppi.
Another key outcome of the project was the conceptualisation for extrinsically guiding the self-organisation of stem cells into functional organoids-on-a-chip devices. “These devices are designed to model the functions of human organs in vitro and allow us to attain more physiologically relevant organoid shapes, sizes and functions,” notes De Coppi.
A step change in treating SBS
All the INTENS project outcomes represent a step change in treating SBS. “The implication of these results is so relevant to the field that Nature Medicine decided to run an editorial on the topic, and Nature Reviews Gastroenterology & Hepatology a Research Highlight,” says De Coppi. “This is in addition to both publications having already published our results.”
Most importantly, this project’s work will ultimately result in better treatment for SBS patients. “Not only will this make treatment much more affordable and accessible for SBS patients, it also has the potential to substantially improve their prognosis and their standard of life,” concludes De Coppi.
The team is currently working to advance these results towards commercialisation and clinical translation.