Beating diabetes: strategies to improve pancreatic islet transplantation

Type 1 diabetes is a chronic disease that is caused by nearly complete destruction of insulin producing beta-cells in the islets of Langerhans, affecting approximately 25 million people worldwide. Prior to the discovery of insulin, diabetes most certainly led to death. To date, patients with type 1 diabetes require daily insulin injections to control their blood glucose levels. Although this therapy is effective, it lacks precise glycemic control which on the long term increases the risk of developing life-threatening diseases such as heart disease, stroke, and kidney failure. Patients with type 1 diabetes who have had a kidney transplant or who suffer from severe hypoglycemia unawareness might benefit from intrahepatic transplantation of donor islets, according to the so-called ‘Edmonton protocol’. This procedure has worldwide been conducted over 750 times. Although the initial results are promising, only 10% of patients remained insulin-independent five years after treatment, which together with a lack of sufficient quantities of donor tissue and the need for lifelong immunosuppressive therapy have hampered its widespread application. This thesis describes several strategies that aim at improving the current pancreatic islet transplantation procedure.