Objective
Aim 1: Optimisation of islet seeding into the skin transplant site using our in house developed 3D printing technology
Aim 2: Translation of the findings from Aim 1 into our established pre-clinical model as the precursor to future human clinical trials.
Background Rationale
Type-1 Diabetes (T1D) is an autoimmune disorder caused by the immune destruction of islet cells which affects over 130,000 Australians and is on the rise, with eight newly diagnosed patients identified each day and prevalence increasing at 3 times the population growth in Australia. In addition, we know that up to 40% of patients living with T1D have experienced complications arising from T1D and improving glucose control will reduce and/ or delay the development and progression of these complications. Islet-cell-transplantation (ICT) is an established treatment for hypoglycaemic (low blood sugar) unawareness for individuals living with T1D that is available in Europe, the United Kingdom and Australia. As ICT is currently practiced, human islets from an organ donor are transplanted into the liver, however, up to 75% of islets die within the first 48 hrs. Once the islets enter the liver it is not possible to monitor them and they can't be removed or retrieved, making it difficult to detect and treat islet cell rejection. It is because of these shortcomings that transplantation into the liver of other alternative islet cell types currently being developed, is not approved. Primarily due to regulatory concerns centering on the lack of retrievability of the transplanted cells should a safety concern arise after transplantation. The pipeline for alternative sources of islets is extremely promising and includes : genetically modified human islet cells, pig islet cells and manipulated stem cell products such as stem cell derived islets. All of which can be safely transplanted into the 'in the skin' site developed by our group. With proof that the newly developed 'in the skin' site can support islet survival, with evidence of islet function out to >2.5 years, our focus now moves to maximising the efficiency of islet delivery into the skin. This will ensure that the maximum number of islets transplanted 'into the skin' survive the transplant procedure, increasing the functional capacity of the transplanted cells both of which increase the chance of curing the patient of type 1 diabetes. In order to achieve this we will use 3D printing technology to deliver the islets into the skin precisely positioned to take maximum advantage of the newly created blood vessels that will support their survival and function.
Description of Project
The primary aim of the project is to optimise the delivery process for transplanting islets 'into the skin'. We have previously developed and tested a new technology for transplanting islets into the skin. This requires making a small wound in the skin and inserting a special material that promotes the formation of new blood vessels. These new blood vessels allow the islets to survive in the skin and more importantly to function, by sensing changes in blood glucose levels and releasing two hormones called "insulin" and "glucagon" whose roles are to increase or decrease blood glucose as required. In order to maximise the number of islets that survive in the skin after transplantation we have developed several new methods/ technologies that we would like to test in this project. They involve the use of special liquids called "BioInks" that allow us to 3D print the islets onto the newly created blood vessels in the skin, ensuring they are evenly spread to maximise their survival and optimise their function. Following optimisation of the delivery process, we hope to achieve equivalent or better transplant outcomes compared to the current best practice which involves transplanting the islets into the liver.
Anticipated Outcome
If successful, this project will establish our newly developed 'in the skin' transplant process as an attractive alternative to the currently practiced islet transplantation into the liver. As such, it will also provide a platform to test in human clinical trials the efficacy of the alternative sources of islet cells that are currently being developed. These improvements would result in an islet transplant therapy for treating type 1 diabetes that is not limited by supply of islet cells expanding this treatment option to a larger cohort of type 1 diabetic patients.
Relevance to T1D
The research proposed in this grant application has the potential to provide a functional cure for type 1 diabetes. This would have significant impacts on the quality of life of people living with this disease. It would free them up from the rigors of daily blood glucose monitoring and insulin therapy, reduce the risk of health complications resulting from long-term type 1 diabetes and allow them to live a normal life without the constant worry and fear that is experienced by people currently living with this disease.