This study, funded through the Pseudo Obstruction Research Trust, aims to demonstrate enteric neurogenesis by human enteric glia. The team will use fresh human intestine for systematic development in a step-by-step manner. The newly-formed neurons will be characterized by qPCR and immunohistochemistry.
They will then compare the characteristics of the newly-formed neurons with adult neurons isolated from a freshly-digested human colon. Finally they will look to understand how the migration patterns of human enteric neurons can be manipulated. To support this they will use human isolated colon and measure enteric neural migration and neurite outgrowth from neural precursors.
| What is neurogenesis? | It is the process by which nervous system cells (neurons) are produced by neural stem cells. |
| What are glia? | Glia are cells in the central nervous system that support the function of the neurons. |
| What is neurite outgrowth? | The process by which projections develop from neuron cells. |
| What is a precursor cell? | A cell in the process of development between stem cell and a fully differentiated cell. |
The researchers
The team is being led by Professor Joanne Martin, Professor of Pathology at the Blizard Institute, Queen Mary University of London.
Why study the potential of developing neurons for tissue repair?
Each year around 170 babies are born in the UK with Hirschprung’s disease.* This means that the neurons in their guts don’t form properly. Other children develop bowel dysfunction as they grow, known as chronic intestinal pseudo obstruction (CIPO). In adults CIPO can result from injury or disease.
This dysfunction of the digestive system means that patients are unable to digest food or pass stools, some even have trouble swallowing. Effectively food gets parked in the digestive system when in a healthy person it is continually moved through by a motion called peristalsis. Symptoms include pain, nausea and vomiting and bloating. There are few options currently for these patients, some of whom require enteric feeding of a liquid nutrient dense diet so that at least some nutrition is possible. CIPO can be life limiting.
The possibility of developing a therapy that could seed and migrate new functioning nerve cells could have a significant impact on the quality of life of these patients and could be a lifeline for some of the most poorly.
* Statistic from https://gtr.ukri.org/projects?ref=MR/R002142/1 Accessed 06.10.25
Final Report Summary
Sometimes, babies are born with an inadequate nerve supply in their intestine (e.g. Hirschsprung disease). This means that the intake of food cannot be processed, and feces cannot be excreted. Sometimes in adults, these nerves may also fail to function adequately (causing swallowing difficulties or bowel obstruction). Treatment usually involves surgery. Using mice, one of us is developing methods by which specialised cells within the intestine (known as glial cells, which support the functions of nerves) can be encouraged to grow into nerves. However, it is critical to know that this can also be achieved in humans. The collaboration enabled by this grant overcomes a major barrier by being able to access a regular supply of ‘fresh’, ‘normal’ human intestine (following surgery for bowel cancer). Using these tissues different methods are being developed in a step-by-step manner. We optimised our ability to isolate and culture nerves embedded within the intestine (‘native’ nerves) and we have been developing methods of proving that the nerves retain an ability to function normally and can respond to factors which increase their growth and ability to connect with each other. Additionally, we developed the method of preparing ‘newly-grown’ nerves from their supporting glial cells (a different type of cell which is closely associated with the nerves) to the point at which we now need to prove that the newly-created nerves really are derived from the original glial cells. This requires the development and novel application of different methods for which plans are in place. Once complete, we will compare the two different nerve populations (native vs newly-grown). Each of the techniques has required the development of new and challenging methods. In spite of the major setback caused by Covid-19, we are still hoping to complete this work, possibly by transference of the studies to a PhD student.
Impact of Bowel & Cancer Research (The Pseudo Obstruction Research Trust) funding
Funding from Bowel & Cancer Research enabled us to establish a major collaboration with The Crick Institute. The technique developed by these investigators could then be transferred to the human intestine. This and the other techniques described and developed in this project were highly innovative. As such, the funding from Bowel & Cancer Research allowed us to “seed” this new research.