residual graft function.

Alternative Methods

As the current method of islet allotransplantation has made great progress toward clinical application

over a long period of time, other alternative methods have also advanced. There continues to be a great

deal of interest in the use of encapsulated islets. These capsules can be made from a variety of materials

designed to be permeable enough to permit the passage of insulin and glucose, but to isolate the islet

from the immune system. Several pilot clinical trials in humans, with transplantation into the peritoneal

cavity without immunosuppression have been reported, which confirms the safety of the procedure and

the demonstration of graft function, if not insulin independence.178,179 No allo- or autoantibody has been

detected in this small number of recipients. Human islets can also be shipped safely for long distances

after encapsulation and culture without compromising viability and function.180 The major barriers to

graft function and longevity have been the tendency of the capsules to cluster and fibrose, which limits

their efficacy.

Animal studies suggest that bone marrow precultured with human islets may enhance the survival and

function of transplanted islets, thus significantly improving the therapeutic efficacy of islet

transplantation.181 Other work has cotransplanted mesenchymal stem cells with islets, which may be

beneficial for islet engraftment by promoting cell survival/angiogenesis and reducing

inflammation.182,183

THE FUTURE OF PANCREAS AND ISLET TRANSPLANTATION

Many challenges remain in determining the ideal insulin replacement therapy for type 1 diabetics.

While the current allocation system designed to maximize whole-pancreas transplantation ensures the

most efficient use of donor pancreata, improvements in the efficiency of islet isolation may require that

further refinements be made to allocation policy. Current outcomes support the prioritization of wholepancreas transplantation over islet transplantation, and sufficient long-term survival reproducible

among a larger number of centers may be required before islet transplantation can move further into

the mainstream. If this occurs, the reduced morbidity of islet transplantation may mean that a large

number of candidates who are not surgical candidates for pancreas transplantation may be islet

candidates in the future. Many centers have taken the philosophical step to offer islet transplantation

primarily to diabetics who would not otherwise receive immunosuppression, that is, nonuremic

diabetics. This is somewhat in contrast to PTA transplantation, which is offered to only the most

exceptional candidates. Taken further, islet transplantation could theoretically be open to a large

number of type 1 diabetics that would surely exhaust the limited supply of human donor pancreata.

However, the experience gained by the development of islet transplantation would surely apply to

technologies not affected by donor supply, such as islet xenografts or engineered β-cells, which could

have a profound impact on the devastating effects of diabetes on the public health worldwide.

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