Future Directions

After almost 3 decades of persistent trials, islet transplants are only beginning to contribute in a clinically significant fashion to the treatment of a select group of people with type 1 diabetes. While the success of the Edmonton trial has been considered a turning point, challenges remain. With currently available technology, only half of all pancreata processed for islets now meet release criteria for clinical transplants. Islets from 2 donor pancreata are still required to reliably reverse diabetes. It is reasonable to assume that 4 pancreata are actually required to reverse diabetes, making islet transplants much less effective than vascularized whole-organ transplants, at least for now. The next critical step is to enhanced the viable islet mass retrievable from 1 donor pancreas by optimizing the entire islet isolation process until consistent diabetes reversal after transplants of islets prepared from a single donor pancreas is achieved. This achievement would have a marked impact on pancreas allocation for islet transplants. It would represent a significant boost to the field. Achieving this outcome will also require application of innovative therapies that enhance islet engraftment and early function in combination with new approaches of immunosuppression that minimze the metabolic demand on transplanted islets.

With the development of new immuosuppressive preconditioning and maintenance agents, the immunosuppressive risks now associated with islet transplants will continue to diminish. This will permit a greater number of individuals to be transplanted earlier in the course of their disease without unacceptable immunosuppressive risk. Tissue availability will be the limiting factor in determining the magnitude of the impact of islet transplants on treating diabetes. Until the day that islet preparations can be taken down off the shelf for transplantation, only a small proportion of the millions of persons with diabetes can be treated by cellular replacement. Intense research in developmental and stem cell biology and xenotransplantation aims to achieve those goals.

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