Type 1 diabetes (T1D) is an autoimmune disorder in which the destruction of insulin-secreting β-cells leads to an inability to regulate blood glucose appropriately, leading to a range of pathological consequences. We currently treat the symptoms of T1D with daily administration of exogenous insulin, but recent advances in human islet transplantation protocols offer the potential of a permanent cure for T1D. However, islet grafts are metabolically fragile and graft survival is compromised by the hypoxic, inflammatory host environment, such that up to 70% of graft function is lost in the immediate post-transplantation period. We have shown that mesenchymal stromal cells (MSCs) have beneficial effects on islet graft functional survival in animal models of diabetes, and we have identified a cocktail of MSC-derived molecules that contribute to this. This project will determine whether these beneficial effects translate to clinically relevant human islets and thus have the potential to improve the outcomes of human islet transplantation as a treatment for T1D. This is a translational project in which data generated from experimental studies will be used to improve human islet transplantation as a therapy for type 1 diabetes.
Year 1: Determine whether molecules secreted by human MSCs have beneficial effects on human islet/β-cell survival and function using a range of in vitro functional. We will assess changes in human beta cell gene expression using scRNAseq and bioinformatic analysis. Training will be provided by the supervisors and the School.
Year 2: Assess human islet function in vivo in a novel mouse model of human islet transplantation. Comprehensive training in in vivo techniques will be provided.
Year 3: A route to translation: the student will work with co-supervisor Dr Sufyan Hussain to determine how best to move to work to a clinical setting, offering experience into how the translation process works in the real world.