What is an islet transplant?
Islets are clusters of cells found in the pancreas, including beta cells. Beta cells are the cells that make insulin and they are destroyed in type 1 diabetes (T1D), acting like tiny insulin factories in the body.
An islet transplant involves putting new islets into people with T1D, giving them a new supply of beta cells so that they can make their own insulin again. People who have received an islet transplant often need to give themselves much less insulin shortly after their procedure or may stop needing insulin therapy altogether. For people living with T1D, this can mean fewer dangerous low blood glucose (hypoglycaemia) events and improved quality of life.
However, over time, the immune system can gradually damage the transplanted cells, meaning insulin therapy may be needed again. Many people require more than one transplant to have enough functioning cells, and some may need additional cells in time.
John, who had 18 months without insulin therapy after receiving 3 islet transplants, said:
“I have a lot of freedom now that I didn’t use to. I don’t have hypos overnight anymore, so I don’t have to get up in the middle of the night. And I can now feel when I’m having a hypo and react to it. It’s an absolute blessing. It used to be external insulin keeping me alive, now I know my new islets are keeping me alive and the extra insulin I take is just keeping me going.”
Read more about John’s experience of having islet transplants.
Who can have an islet transplant?
Since 2012, islet transplants using islets from organ donors have been a nationally funded treatment for people with T1D in Australia. But because of the limited availability of organ donors and the risks of the lifelong medications that come with islet transplants, only a limited number of people with T1D qualify to receive the procedure. This includes people who live with T1D who have hypoglycaemic unawareness, a dangerous condition where someone can’t ‘feel’ their blood glucose falling to very low levels.
Islet transplant research
Breakthrough T1D is funding research to address the current challenges associated with islet transplants to make them accessible to more people with T1D. Breakthrough T1D is actively tackling the key challenges limiting islet transplantation through targeted research, partnerships and clinical programs.
The challenge: Broad immunosuppression
People who receive islet transplants must also take medications called immunosuppressants to lower the activity of their immune system and stop it from immediately destroying the newly transplanted islets. But the immunosuppressants currently used dampen the immune system, preventing it from fighting off infections and certain cancers. These medications suppress the entire immune system, which can increase the risk of infections and certain cancers, and may have side effects affecting organs such as the kidneys.
The solution: Limiting immunosuppression
Breakthrough T1D is funding a clinical trial in the US of islet transplants with a more targeted immunosuppressant drug called tegoprubart. The early results are promising, with participants able to make their own insulin without experiencing the side effects seen with classic immunosuppressant drugs. Another clinical trial, supported by Breakthrough T1D through the T1D Fund, has given one person with T1D islets that have been genetically edited to hide from the immune system. The islets are still alive and making insulin over a year later. You can learn more about both trials in this new piece.
Here in Australia, we’re funding promising early career researcher Dr Seigmund Lai, whose research aims to reduce the need for immunosuppressant drugs in islet transplants. He is studying whether more targeted drugs can just reduce immune activity around the transplanted cells, rather than dampening the entire immune system. He is exploring gene editing approaches to help transplanted cells become less visible to the immune system so that they can go undetected and avoid being attacked.
The challenge: Limited supply of islets
Islets for transplants currently come from the pancreas of deceased organ donors. Several organ donors are needed to get enough islets for a transplant for one person with T1D. Because so many donors are needed for each transplant, and each person with T1D may need multiple islet transplants, there are not enough donors for everyone.
The solution: Alternative sources of islets
To offer a larger and more consistent source of islets, researchers are growing islets in the lab using stem cells. Stem cells are cells that can turn into any other cell type in the human body- including insulin-making cells. Breakthrough T1D began funding Professor Doug Melton’s research to figure out how to do this back in 2000 and in 2014, he succeeded. Now, clinical trials are underway in North America and Europe giving people with T1D stem cell-derived islets, with promising results so far.
Breakthrough T1D is funding Professor Wayne Hawthorne to investigate whether islets from pigs could be used in islet transplants to overcome the shortage of human islets. However, pig islets would cause a strong attack from the human immune system that they couldn’t survive, so Professor Hawthorne is genetically editing the islets to avoid triggering this immune reaction. If altering the genes in the donor pig can reduce the post-transplantation immune response, it would also mean that less – or even no –immunosuppressant drugs would be needed.
The challenge: transplant site location
Islet transplants are currently put into the liver, but the environment there is hostile for the new cells and difficult to access for monitoring or removal. So, researchers are looking at alternative transplant sites that are gentler on the transplanted cells and easier to access.
The solution: An alternative transplant site
Professors Toby Coates is placing islets from organ donors inside a biodegradable material called a BTM, which is typically used to treat severe burns. The BTM provides a scaffold that helps form a network of blood vessels to support the transplanted cells. The BTM with the islets inside is placed into the skin in patients’ arm, which is a more accessible location for topping up with more cells or removing the transplant
Professor Toby Coates said: “Our research project is aiming to create a future where more people with T1D can access islet transplants, so that they will be able to make insulin for themselves again. The BTM is inserted into the inner upper arm and will completely break down over time, but the blood vessels it has stimulated to be created will remain. So, it leaves beautiful blood vessels behind that can support and nourish islet cells in a location where they can be easily monitored and removed if necessary.”
Alec Tibbet, the first person to receive this new type of islet transplant, said: “I’m still on my insulin pump but my insulin needs have significantly reduced. I don’t get the incredibly high or incredibly low glucose levels anymore, and I don’t get the symptoms.”
Learn more about this exciting research project.
Our role in accelerating progress
Breakthrough T1D doesn’t just fund research. We help connect the science, clinical infrastructure and global partnerships needed to move therapies forward faster. Through initiatives like the Islet Transplant Program and the Australasian Pancreas and Islet Network (AUSPIN), we are building the pathways required to translate islet transplantation from research into impact the lives of people with T1D.
Find out more about our research to cure T1D.