Modulation of Early Inflammatory Reactions to Promote Engraftment and Function of Transplanted Pancreatic Islets in Autoimmune Diabetes

We acknowledge that successful long-term islet survival in the liver and immune tolerance to intrahepatic islet antigens are highly dependent upon the initial inflammatory and priming events that occur at this site. Thromboembolic and necroinflammatory events occurring in the liver early after portal vein islet transplantation are thought to reduce the total islet mass by up to 75%. The magnitude of such loss represents a major factor necessitating the extremely large number of islets needed to achieve normoglycemia. A better understanding and control of these events including their likely support to effector immune responses - are required if we are to develop ways to prevent them, improve intrahepatic islet engraftment, and achieve long-term tolerance.