One of the most challenging clinical disorders to manage is enteric neuropathy, when the gut stops functioning due to damaged neurons and the muscles in the intestinal system. There are approximately 500 million neurons distributed along the entire bowel. Enteric neuropathy is a term used to describe a range of conditions such as Hirschsprung disease, hypertrophic pyloric stenosis and Chagas disease. Patients suffer severe and constant pain, nausea, vomiting and other digestive problems. There is no cure and treating the symptoms often includes surgery.
Could stem cells repair or replace the damaged or missing neurons? Over the last two decades, numerous international groups have been involved in studies to find out if it could be possible to develop stem cell therapy.
At the fourth international meeting ‘Development of the enteric nervous system; cells, signals, genes and therapy’ held in Rotterdam, the Netherlands in April 2015, a multidisciplinary group of basic scientists and clinicians, including surgeons, gastroenterologists, and pathologists, decided that a White Paper should be written aiming to form a consensus and provide scientists in the field with protocols for working with the specific stem cells associated with the nervous system of the gut.
Crick Group Leader, Professor Vassilis Pachnis, who heads up the Development and Homeostasis of the Nervous System Laboratory at the Crick (Mill Hill) collaborated with lead author, Dr Alan Burns (Institute of Child Health, UCL) and others to write the White paper on guidelines concerning enteric nervous system stem cell therapy for enteric neuropathies. This Paper sets out experts’ views on the research methods, transplantation into the bowel, and the assessment of transplant success. It also highlights obstacles that must be overcome in order to progress from successful preclinical studies in animal models to ENS stem cell therapies in the clinic.
The last decade has yielded significant progress in the field of stem cell therapies for enteric neuropathies. There is now a critical mass of researchers addressing the many challenges that remain and validating emerging techniques and findings.
Ultimately, successful transplantation of stem cells into the gut will be defined by an improvement in the function of the gut. The safety of stem cell therapy must also be assessed. Considerable interaction between the research community and regulatory groups will be required to determine specification and quality standards. But for the first time this has brought a real prospect of clinical application and ‘first in man trials’.