Intraportal islet transplantation has a long history as a procedure for clinical islet transplantation. However, many recent studies revealed that the intraportal procedure has some disadvantages in transplant efficiency and safety. Many candidates as an optimal transplant site for islets have been assessed, but further studies and clinical trials are still necessary. Intramuscular and subcutaneous spaces are important candidates, because the transplant and biopsy procedures are simple approaches with minimal invasion and few complications. Although they are sites with hypovascularity and hypoxia, which contribute to the poor transplant efficiency, many experimental trials for improving the outcome in intramuscular and subcutaneous islet transplantations have been performed, focusing on early angiogenesis and scaffolds for engrafting transplanted islets. We review current progress in intramuscular and subcutaneous islet transplantations and discuss ways to develop them as optimal transplant sites for islets.
Due to current improvements in techniques for islet isolation and transplantation and protocols for immunosuppressants, islet transplantation has become an effective treatment for severe diabetes patients. Many diabetic animal models have contributed to such improvements. In this paper, we focus on 3 types of models with different mechanisms for inducing diabetes mellitus (DM): models induced by drugs including streptozotocin (STZ), pancreatomized models, and spontaneous models due to autoimmunity. STZ-induced diabetes is one of the most commonly used experimental diabetic models and is employed using many specimens including rodents, pigs or monkeys. The management of STZ models is well established for islet studies. Pancreatomized models reveal different aspects compared to STZ-induced models in terms of loss of function in the increase and decrease of blood glucose and therefore are useful for evaluating the condition in total pancreatomized patients. Spontaneous models are useful for preclinical studies including the assessment of immunosuppressants because such models involve the same mechanisms as type 1 DM in the clinical setting. In conclusion, islet researchers should select suitable diabetic animal models according to the aim of the study.
Our data provide evidence for the role of NFκB in the pathogenesis of chronic pancreatitis, and strongly suggest that WA could be used as a potential therapeutic drug to alleviate some forms of chronic pancreatitis.
Islet transplantation could become an ideal treatment for severe diabetes to prevent hypoglycemia shock and irreversible diabetic complications, once some of the major and unresolved obstacles are overcome, including limited donor supplies and side effects caused by permanent immunosuppressant use. Approximately 30 years ago, some groups succeeded in improving the blood glucose of diabetic animals by transplanting encapsulated islets with semi-permeable membranes consisting of polymer. A semi-permeable membrane protects both the inner islets from mechanical stress and the recipient's immune system (both cellular and humoral immunities), while allowing bidirectional diffusion of nutrients, oxygen, glucose, hormones and wastes, i.e., immune-isolation. This device, which enables immune-isolation, is called encapsulated islets or bio-artificial pancreas. Encapsulation with a semipermeable membrane can provide some advantages: (1) this device protects transplanted cells from the recipient's immunity even if the xenogeneic islets (from large animals such as pig) or insulin-producing cells are derived from cells that have the potential for differentiation (some kinds of stem cells). In other words, the encapsulation technique can resolve the problem of limited donor supplies; and (2) encapsulation can reduce or prevent chronic administration of immunosuppressants and, therefore, important side effects otherwise induced by immunosuppressants. And now, many novel encapsulated islet systems have been developed and are being prepared for testing in a clinical setting.
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