Important step forward in stem cell therapy for rare bowel disease

Hirschsprung disease is a rare condition where some nerve cells are missing in the large intestine. This means the intestine cannot contract or move stool and therefore can become blocked. This can cause constipation and sometimes lead to a serious bowel infection called enterocolitis.

Around 1 in 5,000 babies are born with Hirschsprung disease. The condition is usually picked up soon after birth and treated with surgery as soon as possible; however patients frequently suffer debilitating, lifelong symptoms, with multiple surgical procedures often required.

For the first time, researchers have now used stem cell therapy in human tissue from people with Hirschsprung disease to generate nerve cell precursors, which then produce the missing nerves in the intestine after transplantation. This in turn should improve the intestine’s functionality. It is hoped the discovery could lead to improved symptoms and better outcomes for individuals with the disease.

Dr Anestis Tsakiridis, Principal Investigator from the University of Sheffield’s School of Biosciences said: “Our findings have laid the foundations for the future development of a cell therapy against Hirschsprung disease and we will continue our efforts to bring this to the clinic in the next few years.

“This has been a fantastic collaboration, led by two talented early career scientists, Dr Ben Jevans and Fay Cooper.”

The research, published in Gut and funded by the Medical Research Council, is a collaborative effort between researchers at the University of Sheffield and UCL which began in 2017.

Researchers at the University of Sheffield focused on the production and analysis of nerve precursors from stem cells. These were then shipped to the UCL team, who prepared the patient gut tissue, undertook the transplantation and maintenance of the tissue and then tested the function of the tissue segments.

The study involved taking tissue samples donated by GOSH patients with Hirschsprung disease as a part of their routine treatment, which were then cultured in the lab. The samples were transplanted with stem cell-derived nerve cell precursors which then developed into the crucial nerve cells within the gut tissue.

Importantly, the transplanted gut samples showed increased ability to contract compared to control tissue, suggesting improved functionality of the gut in those with the disease.

Principal Investigator, Dr Conor McCann from UCL Great Ormond Street Institute of Child Health, added: “This study is a real breakthrough in our cell therapy work for Hirschsprung disease. It really shows the benefit of bringing the expertise of different groups together which will hopefully benefit children and adults living with Hirschsprung disease in the future.”

Researchers will now be applying for further funding for clinical trials to develop this treatment.