Australia has three Islet Transplantation Centres (ITC), but only two islet isolation facilities. That means that precious donated islets sometimes have a way to go to get to their destination. Australian researchers have specially designed ‘egg cartons’ to provide oxygen and physically separate the islets, keeping more of them alive during transport.
What is islet transplantation?
Islet transplantation involves implanting insulin-producing islet cells from a human donor into the liver of a person with type 1 diabetes (T1D). The aim is to reduce the frequency and severity of hypoglycaemic episodes (hypos) and potentially achieve insulin independence. Usually, more than one islet transplant is needed to maintain these benefits, and immunosuppressant drugs to prevent the body attacking the implanted cells are also part of the therapy. Because of this, islet transplantation is currently limited to people who have unstable T1D, particularly those with hypo unawareness who suffer recurrent and severe hypo episodes.
The transplant process is minimally invasive and the islets are administered into the portal vein – a large vein in the liver – under local anaesthetic. More than 50 Australians with T1D have successfully received donor islets since the program began.
The challenges of transporting fragile islets
Transplants rely on islets from the pancreas of a matched donor. Donor islets are a precious gift, and the process to isolate islets from a deceased donor is a long and intensive one. The process takes place in one of Australia’s two special facilities in Sydney and Melbourne. Then, the islets are shipped off to the closest transplant facility to the recipient.
Unfortunately, between 20-40% of the islets can die after the isolation process, during storage and transport. Once separated from the pancreas, islets are extremely fragile, and still need a lot of nutrients and oxygen. Without these, the cells can’t generate insulin and other hormones which help regulate blood glucose levels.
Currently, islets are transported in bags where the islets are floating freely in a solution composed of the required cell nutrients. As the bags move, islets are shaken and bounce onto each other. These interactions can destroy the islets.
The ‘egg carton’ breakthrough Improving the survival of islets pre-transplantation is one of the many current areas of research which aim to make islet transplantation more widely available. An all-Australian team including Director of St Vincent’s Institute Melbourne Professor Thomas Kay, as well as JDRF-funded researchers Professor Toby Coates, Dr Thomas Loudovaris, Associate Professor Shane Grey and Associate Professor Helen Thomas have designed and used the ‘egg carton’ technology to successfully transport both human and animal islets between Melbourne and Adelaide by plane. The islets are held in place by a membrane that allows passage of oxygen and nutrients. The journey takes on average six hours door-to-door and the egg cartons have been able to maintain islet cell mass and function. The research team also tested different sizes of the carton to discover the optimal size for long trips.
This research is a crucial step to increase the number of successful transplantations, reduce costs, and to reduce the number of isolations required to enable a single transplant. Translating this technology to the clinics is the next step to improve islet survival during shipping. The ‘egg carton’ technology will also need to be produced in greater numbers to accommodate the hundreds of thousands of islets required for each transplant recipient.
Ongoing islet transplantation research While islet transplantation is a safe procedure, there is need for more research on all aspects to refine it further and make it available to even more people. This current research tackles the pre-transplantation phase; however there still remains room to improve the post-transplantation stage too. For example, we want to find ways to implant new cells without the immune system attack. To make the procedure available for more people, including children, we also need to find a way to reduce or remove the need for immunosuppressive drugs. Currently, all transplants need human donors, so we need to find ways to produce an endless supply of insulin-producing cells, from stem cells or from other cells already found in the pancreas.
To achieve this, there is a vast amount of ongoing research, in Australia and globally. JDRF- funded research includes encapsulation techniques to protect islets such as artificial skin and membrane systems, encouraging stem cells to behave like beta cells and modification of islet cells to allow them to fend off the immune system attack. The T1DCRN is funding a large trial investigating drug-free approaches to immunosuppression to protect implanted islets. This is led by Professor Philip O’Connell and the Westmead group.
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