Experimental islet transplantation started more than 3 decades ago with the discovery that islets of Langerhans could be separated from the pancreatic tissue with collagenase. Islet allotransplantation could potentially replace pancreas transplantation for the treatment of Type 1 diabetics. Islet autotransplantation can be used to prevent diabetes mellitus following a major pancreatectomy. As of today 400-500 islet allotransplantations and 200-300 autotransplantations have been performed worldwide.
The success of islet transplantation in humans is limited, with no more than 20% of patients achieving complete normalization of glucose metabolism. The long-term function of transplanted islets has been poor with most grafts showing deterioration in function within 5 years.Â
The main obstacles to successful islet transplantation are: a) relatively small beta cell mass available after islet purification, b) autoimmune and alloimmune islet cell destruction, c) current use of diabetogenic immunosuppressants.
The main mode of islet transplantation consists of intraportal embolization. Other potential sites for transplantation include the spleen and the kidney capsule.
The morphological aspects of allo- and autoimmune islet graft destruction are well known through experimental studies. These consist of lymphocytic isletitis and eventual disappearance of the hormone producing cells. In clinical practice tissue evaluation is not used for the diagnosis of islet rejection. In experimental studies sophisticated methods for the detection of islet rejection have included the demonstration in serum of elevated levels of endogenous islet proteins and daily sequential intravenous glucose tolerance tests.
In addition to islet transplantation, other strategies for treatment of type I diabetes are being investigated. These include fetal pancreas transplants, genetically engineered beta-cell lines and gene therapy, implanted insulin pumps and artificial pancreas units. Xenotransplantation (i.e. porcine islets) or in vitro expansion of cultured beta-cells could in theory represent the solution for the problem of limited pool of islet tissue for transplantation.
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