- Dr Karen Dwyer, Principal Investigator
- Prof. Tom Kay, Co-Investigator
- Dr Jennifer McRae, Senior Research Associate
- Ms Joanne Chia, PhD Student
- St. Vincent’s Hospital, Melbourne, Australia
- Prolonging Pancreatic Islet Cell Survival following Transplantation
Type 1 diabetes (T1DM) is a disease of the young, which manifests as an inability to control blood sugar levels and is lethal unless treatment with insulin is instituted. Failure to adequately treat T1DM results in complications and premature death. Islet cell transplantation is an approach to cure T1DM. Clinically, islet transplantation is limited because a large number of islets are needed to be transplanted to maintain adequate insulin levels. Islets are isolated from the pancreas and injected into the vein that leads to the liver. This triggers inflammation and clot formation, which destroys many of the islet cells in the blood vessel. Islets that survive the journey to the liver are then subject to rejection and inflammation. This project aims to examine ways to improve islet viability following isolation and transplantation thus preserving islet cell function in the long term. CD39 is an enzyme that is expressed on blood vessels and has an important role in regulating clotting and inflammation. We have generated mice that overexpress CD39 on islets and can show that these animals are resistant to the onset of diabetes, whereas animals that are lacking this enzyme develop earlier disease. We can also show that when islets expressing CD39 are mixed with blood, clotting is prevented. Together, this suggests that CD39 may mitigate inflammation and recurrent disease that can occur following transplantation. The aims of this work are to examine the effect of CD39 in islet transplantation. We will initially look at a mouse model of islet transplantation before examining the effect of CD39 on human islets. We anticipate that the expression of CD39 on islets will promote survival, which will translate into a greater life span of transplanted islets and thus reduce the number of islets required for transplantation.