Clinical islet transplantation at the University of Alberta--the Edmonton experience. 2005

Wayne Truong, and Jonathan R T Lakey, and Edmond A Ryan, and A M James Shapiro
Clinical Islet Transplant Program, University of Alberta, Edmonton AB, Canada.

While the field of islet transplantation has evolved over the past 30 years and exponential progress and increase in clinical activity has occurred during the past 5 years, it is clear that major challenges still remain, particularly in understanding why islet function seems to decay over time. High one-year rates of insulin independence, and high 5-year rates of partial islet function (with C-peptide secretion and protection from hypoglycemia) are now routine. Improved control of glycated HbA1c and reduced risk of recurrent hypoglycemia are benefits of islet transplantation irrespective of the status of insulin independence. If complete and sustained freedom from insulin is the primary objective, it is clear that whole pancreas transplantation still offers far superior metabolic reserve. However, the less interventional nature of islet infusion and avoidance of major surgery are advantages of islet transplantation over whole pancreas strategies. While the anti-rejection drugs available today may have had an acceptable safety profile in most islet transplant recipients, the drug-related and dose-limiting side effects have proved to be a challenge in some patients. Current islet-alone transplantation requires lifelong immunosuppression and is limited to patients with recurrent severe hypoglycemia and severe labile diabetes. More effective treatments are needed to control both acute rejection and recurrent autoimmunity. Remarkable opportunities lie ahead for improved islet survival, better engraftment and the possibility of expansion of islet mass both in culture and possibly within the patient after transplantation. Living-donor islet transplantation offers one option to expand the available donor supply, but remains controversial because of the potential for diabetes induction or other morbidities in a healthy donor. The development of less toxic immunosuppression and perhaps immunological tolerance will one day also have a huge impact on this field. Alternative tissue sources from either xenogenic sources or stem cells will ultimately solve the challenge of limited donor supply.

UI MeSH Term Description Entries
D007166 Immunosuppressive Agents Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of T-CELLS or by inhibiting the activation of HELPER CELLS. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of INTERLEUKINS and other CYTOKINES are emerging. Immunosuppressant,Immunosuppressive Agent,Immunosuppressants,Agent, Immunosuppressive,Agents, Immunosuppressive
D007515 Islets of Langerhans Irregular microscopic structures consisting of cords of endocrine cells that are scattered throughout the PANCREAS among the exocrine acini. Each islet is surrounded by connective tissue fibers and penetrated by a network of capillaries. There are four major cell types. The most abundant beta cells (50-80%) secrete INSULIN. Alpha cells (5-20%) secrete GLUCAGON. PP cells (10-35%) secrete PANCREATIC POLYPEPTIDE. Delta cells (~5%) secrete SOMATOSTATIN. Islands of Langerhans,Islet Cells,Nesidioblasts,Pancreas, Endocrine,Pancreatic Islets,Cell, Islet,Cells, Islet,Endocrine Pancreas,Islet Cell,Islet, Pancreatic,Islets, Pancreatic,Langerhans Islands,Langerhans Islets,Nesidioblast,Pancreatic Islet
D009926 Organ Preservation The process by which organs are kept viable outside of the organism from which they were removed (i.e., kept from decay by means of a chemical agent, cooling, or a fluid substitute that mimics the natural state within the organism). Organ Preservations,Preservation, Organ,Preservations, Organ
D009927 Tissue and Organ Procurement The administrative procedures involved with acquiring TISSUES or organs for TRANSPLANTATION through various programs, systems, or organizations. These procedures include obtaining consent from TISSUE DONORS and arranging for transportation of donated tissues and organs, after TISSUE HARVESTING, to HOSPITALS for processing and transplantation. Organ Procurement,Organ Procurement Systems,Organ Shortage,Tissue Procurement,Tissue Shortage,Donor Cards,Organ Donation,Required Organ Donation Request,Required Request,Tissue Donation,Donor Card,Organ Donations,Organ Procurement System,Organ Procurements,Required Requests,Shortage, Tissue,Tissue Donations,Tissue Procurements,Tissue Shortages
D003922 Diabetes Mellitus, Type 1 A subtype of DIABETES MELLITUS that is characterized by INSULIN deficiency. It is manifested by the sudden onset of severe HYPERGLYCEMIA, rapid progression to DIABETIC KETOACIDOSIS, and DEATH unless treated with insulin. The disease may occur at any age, but is most common in childhood or adolescence. Diabetes Mellitus, Brittle,Diabetes Mellitus, Insulin-Dependent,Diabetes Mellitus, Juvenile-Onset,Diabetes Mellitus, Ketosis-Prone,Diabetes Mellitus, Sudden-Onset,Diabetes, Autoimmune,IDDM,Autoimmune Diabetes,Diabetes Mellitus, Insulin-Dependent, 1,Diabetes Mellitus, Type I,Insulin-Dependent Diabetes Mellitus 1,Juvenile-Onset Diabetes,Type 1 Diabetes,Type 1 Diabetes Mellitus,Brittle Diabetes Mellitus,Diabetes Mellitus, Insulin Dependent,Diabetes Mellitus, Juvenile Onset,Diabetes Mellitus, Ketosis Prone,Diabetes Mellitus, Sudden Onset,Diabetes, Juvenile-Onset,Diabetes, Type 1,Insulin Dependent Diabetes Mellitus 1,Insulin-Dependent Diabetes Mellitus,Juvenile Onset Diabetes,Juvenile-Onset Diabetes Mellitus,Ketosis-Prone Diabetes Mellitus,Sudden-Onset Diabetes Mellitus
D005500 Follow-Up Studies Studies in which individuals or populations are followed to assess the outcome of exposures, procedures, or effects of a characteristic, e.g., occurrence of disease. Followup Studies,Follow Up Studies,Follow-Up Study,Followup Study,Studies, Follow-Up,Studies, Followup,Study, Follow-Up,Study, Followup
D006085 Graft Survival The survival of a graft in a host, the factors responsible for the survival and the changes occurring within the graft during growth in the host. Graft Survivals,Survival, Graft,Survivals, Graft
D006785 Hospitals, University Hospitals maintained by a university for the teaching of medical students, postgraduate training programs, and clinical research. University Hospitals
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000416 Alberta A province of western Canada, lying between the provinces of British Columbia and Saskatchewan. Its capital is Edmonton. It was named in honor of Princess Louise Caroline Alberta, the fourth daughter of Queen Victoria. (From Webster's New Geographical Dictionary, 1988, p26 & Room, Brewer's Dictionary of Names, 1992, p12)

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