Improving islet transplants to treat type 1 diabetes

For the first time, we are co-funding a research project with the Medical Research Council (MRC). Together, we are supporting Daniel Doherty to complete his PhD, which will focus on improving the outcome of islet transplants for people with type 1.

What are islet transplants?

The islets in the pancreas are home to the insulin-producing beta cells, which are destroyed in type 1. Islet transplants take islets from donated pancreases and put them into the livers of people with type 1. They are only available to people who are really struggling to manage their type 1 due to the risks associated with the immunosuppressant drugs required. Even with the low numbers of people who need islet transplants, there are not enough organ donors for everyone.

Why is Breakthrough T1D UK funding this research?

Currently, several organ donors are needed to gather enough islets for just one transplant. This is partly because many islets don’t survive the transplant. Even the cells that do survive only last a few years, when patients will need another islet transplant. Dan’s research aims to combat this by creating a more supportive environment for islet cells in the liver to boost their survival. This will help people who receive islet transplants produce insulin more effectively and require transplants less frequently. It will also enable more people to benefit from islet transplants.

Studying the liver environment

Using sophisticated techniques, Dan is learning more about how transplanted islets and their neighbouring cells in the liver influence each other. Islets are placed into the liver because it is much easier to get to than the pancreas, which is tucked deep inside the body. Dan is investigating how the liver responds to islets being placed there and why many islets don’t survive.

Researcher Daniel Doherty in the lab

Damage to the surrounding cells

Through his careful research, Dan has identified patterns in the extracellular matrix around the islets and signs of liver injury. The extracellular matrix is a complex network of molecules outside of cells, which link together to form the structure of organs. Fibroblasts are a type of cell that produces key components of this extracellular matrix. Dan is growing pancreatic islets along with fibroblasts in his lab to learn more about how they interact. He thinks this could provide important information about how he can make islets last longer and work better.

Mimicking the pancreas environment

Dan will look carefully at pancreas samples from people without type 1 to understand which cell types are present and how they support the islets. He will compare this with the cells that he has found around the islets once they are in the liver. This will tell Dan which cells could be transplanted with the islets to help support them in the liver.

Research applicable to stem cell therapies

Aside from improving islet transplants, Dan’s findings are transferable to stem cell-derived therapies, where scientists grow insulin-producing cells in their labs from stem cells, which can develop into lots of other cell types. Dan’s research will provide useful insight to boost these cells’ function and survival. Most other research in this area aims to generate as many high-quality insulin-producing cells as possible. Dan’s focus on the supportive structures is crucial for creating healthier islets and supporting them once they have been transplanted into people with type 1.

How will this research help people with type 1?

Dan’s work will help people with type 1 who need islet transplants as well as supporting cure research of stem cell therapies. If more islets can survive both types of treatment, the people with type 1 who receive them will be able to produce insulin more effectively. In the short-term, this research will help limit the number of repeat islet transplants required, making them available for more people with type 1. In the long-term, we hope Dan’s research will contribute to improving stem cell therapies as a cure for type 1.

Take part in islet transplant research

Alongside this project, Dan is interviewing people with type 1 who have received or are waiting to receive a pancreas transplant to help more people benefit from the treatment. He is developing a guide for doctors to maximise the number of transplants from available donors. If you would like to help Dan improve pancreas transplant surgery in the UK, email him on daniel.doherty@postgrad.manchester.ac.uk

Is Breakthrough T1D UK funding any other research like this?

We are funding Dr Rocio Sancho to develop a supportive gel to grow beta cells in. Like Dan, Rocio aims to create an environment that mimics the human pancreas to improve the quality of her beta cells. While Dan is focusing on islets from organ donors, Rocio is growing her beta cells from stem cells in an artificial growth gel.