Published online 5 April 2016 in
Developmental Biology
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'.