Islet cell transplantation

Abstract

The discovery of insulin changed the course of history in the treatment of diabetes. However, despite tremendous progress in insulin formulations and treatment strategies, insulin treatment still cannot fully prevent chronic complications and intensive insulin treatment to improve metabolic control, has often paralleled an increased risk of severe hypoglycemia. A cure for Type 1 diabetes should include: ? Restoration of self tolerance, to prevent recurrence of autoimmunity ? Restoration of physiologic metabolism by replacement of the biologic function (insulin producing cells) that was partially of completely impaired as a result of the disease process. ? Prevention of destruction of the new insulin producing cells by the recipient immune system in the absence of any treatment that could introduce an additional risk to the patient, which could be comparable to, or higher than the risk imposed by disease progression under exogenous insulin treatment. Pancreatic islets could be considered an ideal and more physiologic alternative to insulin, as they can restore metabolic control after transplantation, preventing the development of chronic complications. In fact, islets are capable of perfectly timed insulin release and can keep glucose levels in the normal range, functioning for an entire lifetime, if they are not destroyed by the recipient's immune system. Significant progress has been recently reported in the translational research approach towards the development of a cure for Type 1 diabetes. There is now strong evidence for the technical feasibility of human islet isolation and purification procedures. Proof of function of isolated human islets has been clearly established both in animal models and in pilot clinical trials of human islet allotransplantation in patients with surgical and Type 1 diabetes. Additional research in now needed to improve the current clinical results in terms of long term prevention of rejection and recurrence of autoimmunity, the development of safe, non diabetogenic immunomodulation strategies and ultimately the achievement of donor specific immune tolerance. If success will be achieved in these areas, then we will face the critical challenge of identifying sufficient and suitable sources of insulin producing tissue to treat the increasing number of patients who could benefit from this form of therapy and which would not be limited to Type 1 diabetes. That is why the work on xenogeneic islets, embryonic and adult stem cells, islet regeneration and proliferation, as well as engineering of insulin producing cells must be continued, to identify the most ideal source of insulin producing tissue that could be utilized on a large scale once the impediments and limitations of immunosuppression will be resolved.