Boosting islet survival after transplantation using immune cells

In her Breakthrough T1D-funded project at the University of Edinburgh, Professor Shareen Forbes will test whether giving immune cells called macrophages with islets results in better islet transplant outcomes. She will also study whether this technique could reduce the dose of anti-rejection drugs that people who have islet transplants need to take.

Challenges with islet transplants

Islet transplants are a treatment for people with type 1 diabetes which involve putting islets (clusters of hormone-producing cells, including the cells that make insulin) from organ donors into the liver of someone else. The therapy can help people living with type 1 make some insulin again, but the procedure is not without its risks and challenges.

Over 60% of islets do not survive transplantation, mainly because of the recipient’s body rejecting the new cells. To combat this, recipients must take anti-rejection drugs (known as immunosuppressants), which increase their risk of infection and cancer.

Why is Breakthrough T1D funding this project?

Because of their low survival rate, lots of islets from multiple organ donors are needed for each islet transplant. There aren’t enough organ donors for everyone, meaning that waiting lists are long and not everyone who needs an islet transplant can have one. Increasing the number of islets that survive transplantation would mean fewer cells would be needed per person and more people with type 1 could benefit from the treatment.

Transplanting islets and macrophages

Professor Shareen Forbes will give mice with type 1 diabetes islet transplants followed by a dose of macrophages. Macrophages are a type of immune cell which digest particles in the body ranging from invading bacteria to dying or cancerous cells. They can help reduce inflammation, fight immune rejection and promote blood vessel formation. Shareen’s team can grow macrophages in their lab that have proved safe in humans.

Her research team will observe the effect of this dual treatment on blood glucose levels. They will also explore the best methods for giving macrophages, and the optimal dose of the cells. If this treatment of islets and macrophages stabilises blood glucose levels in the mice, then the team will see if this effect remains after giving the mice immunosuppressant drugs. The researchers will also test if the dose of immunosuppressants can be decreased with the macrophages.

How will this research help people with type 1?

If Shareen and her team can show that macrophages can boost the survival of islet transplants in mice, the technique could be applied to human islet transplants in the future. This would help more people with type 1 benefit from islet transplants and reduce the dose of immunosuppressant drugs they need to take.

Shareen’s research project could also benefit therapies of islets grown from stem cells, which are cells that can transform into other cell types. Trials of stem cell therapies for type 1 diabetes are ongoing and may be improved in the future by giving macrophages with the lab-grown islets to improve the effectiveness of the treatment and limit the need for immunosuppressants.

Is Breakthrough T1D funding any other research like this?

Together with the Medical Research Council are co-funding Daniel Doherty’s PhD project. Dan aims to improve the survival of islets after transplantation into people with type 1 by creating a more supportive environment for islet cells in the liver.

We are funding another of Shareen’s research projects through the Type 1 Diabetes Grand Challenge, our partnership with the Steve Morgan Foundation and Diabetes UK. In this research project Shareen is testing whether transplanting islets in packages with different combinations of drugs can help them survive and function.