Evaluation of novel therapeutic strategies to enhance islet cell viability for Islet Cell Transplantation

The PhD project focuses on evaluating novel therapeutic strategies aiming at enhancing pancreatic islet cell viability for islet cell transplantation. Islet Cell Transplantation is a life-saving treatment for patients with type 1 diabetes who have lost awareness of their hypoglycaemia. Only small fraction of type 1 diabetics receives this procedure and the islet consortium in Scotland carries out around 10 to 20 islet transplants per year. Islet cell transplantation is limited by the availability and quality of donor pancreases and because islet cells are very susceptible to hypoxic injury and oxidative stress about 2/3 islets are lost shortly after transplant.

This project looks at improving islet viability by delivering a novel class of small molecule KMO inhibitors during machine perfusion to reduce hypoxia induced cell injury. KMO is a mitochondrial outer membrane protein important for the metabolism of tryptophan, which plays a role in inflammation and oxidative stress. Kmo inhibition reduces inflammation alleviate renal ischaemia reperfusion injury and it prevents multi-organ failure in a rodent model of pancreatitis.

Although the ideal future would be generating islets with iPSCs, eliminating the need for immunosuppressants, improving current techniques is absolutely necessary to ameliorate the procedure and improve islet engraftment in the recipient.