The success of p-cell replacement therapy through transplantation of the endocrine pancreas as either whole organ or isolated islets has been steadily increasing over the past decade. The shortage of organs and the need for chronic recipient immunosuppression remain major hurdles, limiting the applicability of allogeneic p-cells transplantation to a wider number of patients with insulin-dependent diabetes. As we better appreciate the complex phenomena involved in the immunobiology of transplantation, better tools to promote engraftment and survival of allogeneic tissues will become available for clinical testing. Implementation of methods to improve cadaveric organ donor preservation and storage may allow for optimization of pancreas use from marginal and/or from nonheart-beating donors, which are currently underused for whole pancreas and islet transplantation (Fraker et al, 2002; Markmann et al, 2003). Alternative sources for p-cells are under evaluation, such as xenogeneic islets and stem cell-derived insulin-producing cells, as they may provide an unlimited supply of tissue for transplantation.

Chronic immunosuppression is currently needed to prevent graft rejection and, possibly, recurrence of autoimmunity. Immunosuppressive drugs may have untoward effects, such as increased susceptibility to infection, neoplasms, and organ toxicity. In addition, some of the drugs currently available can be toxic to p-cells, resulting in chronic loss of graft function (Hering and Ricordi, 1999; Pileggi et al, 2001). A number of protocols for the induction of immune tolerance to transplanted tissues are under investigation in experimental animal models, and promising results have been reported that justify a cautious optimism for their potential clinical applicability in the near future.

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