Research Training Fellowship: Mr David Wilkinson
This research was completed on 31 July 2013
Published on 16 May 2011
Hirschsprung's Disease: could stem cell transplants help babies with this serious bowel disorder?
Each year, Action Medical Research awards these prestigious grants to help the brightest and best doctors and scientists develop their career in medical research. Mr Wilkinson’s grant of £139,980 will fund his two-year laboratory study into the possibility of using stem cells to treat a serious bowel disorder that can threaten babies’ lives.
Around one in every 5,000 babies born alive in the UK has a serious bowel disorder called Hirschsprung’s disease.1 Life-saving surgery is often necessary soon after birth, but many of these babies still experience ongoing problems as they grow up – with infection and incontinence, for example.2,3
Mr David Wilkinson, a talented children’s surgeon, is determined to improve the lives of babies with Hirschsprung’s. Evidence suggests it may be possible to use babies’ own stem cells to treat their disease. Mr Wilkinson is investigating this possibility in the laboratory.
“It is a huge privilege to be working on this project, along with a group of dedicated experts. It makes me feel humble to know that our work, made possible by Action Medical Research, could improve the quality of life of children with Hirschsprung’s disease.”
What's the problem and who does it affect?
When problems continue despite life-saving surgery
Each year in the UK, around 160 babies are born with a serious bowel disorder called Hirschsprung’s disease, which can quickly cause problems.1-4 “Most babies with Hirschsprung’s disease become ill within the first couple of weeks of life,’ explains Mr Wilkinson. ‘They develop a potentially life-threatening bowel obstruction, which causes distressing symptoms including constipation, vomiting and swelling of the abdomen.”
All babies diagnosed with Hirschsprung’s need to have surgery to remove the diseased section of their bowel, however children and adults continue to experience significant problems throughout their life.6
Despite undergoing surgery, the function of the remaining bowel does not return to normal in children with Hirschsprung’s,” says Mr Wilkinson. “This leads not only to problems in the early years, such as repeated episodes of enterocolotis – associated inflammation of the bowel – but also leads to lifelong issues such as incontinence. Twenty per cent of teenagers with the disease report problems with faecal incontinence, and this number may even increase as they move into adulthood.6 They can suffer frequent, unpredictable episodes of incontinence, which can be incredibly disabling at school, socially or even within the work environment.”
Up to 10 per cent of children with Hirschsprung’s require a permanent stoma - an opening in the belly, created surgically, which allows faeces to leave the body.2,5 A pouch, attached to the stoma, must be emptied several times a day. It can be hard to adjust to life with a stoma.
What is the project trying to achieve?
A focus on stem cells
The wall of the bowel normally contains nerves, which trigger muscle contractions, to push digested food along. Babies with Hirschsprung’s are born with an abnormal section of bowel, which does not contain nerves and cannot push food along. Build-up of food in this section causes blockages.
“We believe it may one day be possible to transplant a baby’s own stem cells into the bowel wall, to re-grow the missing nerve supply and improve the function of the bowel,” explains Mr Wilkinson. Certain stem cells have the ability to turn into the right sort of nerves. When these cells are transplanted into experimental sections of bowel in the laboratory, they stimulate contractions.
“I am investigating how these stem cells might behave if transplanted into humans, by studying what controls their growth and development,” says Mr Wilkinson. This is important, as uncontrolled growth could cause cancer. The knowledge gained might also allow the cells’ behaviour to be manipulated, to make any future transplants more effective.
Mr Wilkinson is using stem cells and bowel tissue donated by around 40 babies and children who are undergoing surgery for Hirschsprung’s and for other problems, along with cells from a laboratory model.
What are the researcher's credentials?
|Project Leader||Mr David Wilkinson|
|Location||Department of Reproductive and Developmental Medicine, Institute of Child Health, Alder Hey Children's Hospital, Liverpool and the Department of Cellular & Molecular Physiology, Institute of Translational Medicine, University of Liverpool.|
|Grant awarded||11 February 2011|
|Start date||1 August 2011|
|End date||31 July 2013|
|Grant code||RTF1395, GN1795|
Mr Wilkinson, a qualified doctor, specialised in children’s surgery after moving to Alder Hey Children’s Hospital in Liverpool, one of the largest and busiest specialised children’s hospitals in Europe.
Mr Wilkinson has since joined a research group based at the Institute of Child Health at the University of Liverpool. “While working as a surgical trainee I have come into contact with many children and their families who are having to deal with the long-term complications of Hirschsprung’s disease. So when the opportunity presented itself to help develop a new treatment, designed to improve the lives of children with the disease, I jumped at the chance.”
He believes he is in the ideal position to succeed in this fellowship, under the expert mentorship of Professor David Edgar and Mr Simon Kenny. “The University of Liverpool has a world-class research pedigree. My mentors have been working on Hirschsprung’s disease, the development of the nervous system in the gut, and the potential of stem cells for a number of years. They have made significant progress, as evidenced by an extensive series of world-class publications.”
Who stands to benefit from this research and how?
Stem cell treatment
Mr Wilkinson is in the early stages of developing a new treatment for babies with Hirschsprung’s. If successful, the treatment might also benefit older people with Hirschsprung’s and people who suffer from faecal incontinence for other reasons.
When babies with Hirschsprung’s have surgery, it is not possible to remove absolutely all of the diseased bowel, meaning a small section is left behind. Researchers suspect this might contribute to some of the long-term problems, such as incontinence, that babies can experience while they are growing up.
Mr Wilkinson believes it may one day be possible to spare babies from these ongoing problems, by transplanting certain stem cells into the diseased section of the bowel that remains after surgery. The stem cells can be isolated when the babies undergo surgery and frozen for future use. The theory is that transplants might lead to the growth of new nerves, allowing the bowel to function properly.
“I am incredibly grateful to Action Medical Research for their support in awarding me this fellowship,” explains Mr Wilkinson. “It is an exciting opportunity to move closer to a new treatment for Hirschsprung’s disease, which could eventually improve the lives of both children and their families.”
- Goldberg EL. An epidemiological study of Hirschsprung’s disease. Int J Epidemiol 1984; 13(4):479-84.
- Mills JLA et al. Long-term bowel function and quality of life in children with Hirschsprung’s disease. J Paediatr Surg 2008; 43: 899-905.
- Hirschsprung’s and motility disorders support network. Website accessed 28 April 2011. http://www.hirschsprungs.info/hd.html
- Office for National Statistics. Fertility. Website accessed 2 April 2011. http://www.statistics.gov.uk/cci/nugget.asp?id=951
- Baillie CT et al. Long-term outcome and colonic motility after the Duhamel procedure for Hirschsprung's disease. J Pediatr Surg 1999; 34(2):325-9.
- Rintala, R. J. and M. P. Pakarinen. "Long-term outcomes of Hirschsprung's disease." Seminars in Pediatric Surgery, 2012. 21(4): 336-343.