Understanding the hepatic microenvironment to improve function and survival of transplanted pancreatic islets in diabetes

A patient with Type 1 Diabetes Mellitus (T1DM) administers 65,000 insulin injections and checks their blood sugar 80,000 times during their lifetime. T1DM results from destruction of beta-cells by the body's own defensive cells. Beta-cells are specialist insulin producing cells in the Islets of Langerhans which are hormone producing sections scattered within the pancreas.

Insulin is a signalling molecule which controls blood sugar levels. This destruction, prevents the beta-cells in the pancreas from producing insulin, meaning that blood sugar levels will rise out of control. As a result, patient's need to inject insulin regularly, throughout the day, to control their sugar levels.

This affects approximately 400,000 people in the UK, 29,000 of whom are children with a predicted rise to 600,000 and 48,000 in 2035. Worldwide this figure is approximately 37 million. This represents a significant financial burden for the healthcare system and in 2010/11 the NHS spent £1 billion on direct patient care for T1DM. Severe T1DM can cause loss of vision, kidney failure, strokes and heart disease causing debilitating health problems and death at a young age.

Islet transplantation offers an avenue to help these patients improve their sugar control by replacing the islet cells which have been destroyed. It allows patients to produce insulin again without injections. It involves taking islet cells from the pancreas of an organ donor and separating the insulin producing islet cells out, before adding them to the liver through an infusion.

Islet transplant works well for some patients, but it is not perfect. It can stop patients from having dangerous levels of poor sugar control, but many patients will continue to need additional insulin injections even after islet transplant and some transplants will only work for a short period of time. Most patients will also need to have more than one islet transplant, meaning that less patients can benefit from this treatment as the number of organ donors is very limited.

Many of the islet cells do not survive in the liver after transplant. We will investigate why this happens and how this can be improved, so that islet transplants can work better, for longer, for more people.

We will look closely at islet cells in normal pancreas samples in the laboratory so I can establish the support they receive from other neighbouring cells which encourage them to work well in their normal environment. We will then compare what we discover to samples of islet cell infusions. This will allow us to see what supporting cells and pathways are present after the islets have been separated from their neighbouring cells and the rest of the pancreas.

We will then also compare the islet cell environment after they have been placed into the liver and how the neighbouring liver cells influence islet cell survival and function.

We hope to find ways to create a more supportive environment for islet cells after separation from the pancreas and after transplant, so that more cells survive and produce insulin more effectively. Answering these questions will make islet transplant available for more people as repeat transplants will not be required. Therefore, more patients suffering from the complications of severe T1DM can benefit from this treatment.

Please follow the link to my video for a visual summary of my research. https://youtu.be/bWfo4JknIx8