The relative improvement in outcome for islet transplantation has led to an expansion of clinical islet transplant research worldwide. However, several major hurdles need to be overcome before islet transplantation can be more broadly applied in the treatment of diabetes. The continued general requirement for two donor organs for each islet recipient remains a major limiting factor (32). To this end, further developments in islet isolation technique will, no doubt, continue to improve islet yield. These include the use of a two-layer perfluorocarbon cold storage method for islets isolated from ischemically damaged pancreases (65), the use of antioxidants such as vitamin E to reduce oxidative stress during isolation (66), the use of protease inhibitors during the isolation process to avoid overdigestion of islets (67), and improved pancreas procurement techniques to reduce warm ischemic times (68). Improving initial islet engraftment by reducing early non-specific cytokine-mediated inflammation using agents such as infliximab (anti-TNF-α monoclonal antibody) and etanercept (anti-TNF-α fusion protein) is also a promising area of study.

The development of new immunosuppressive regimens also continues to progress. A recent study of combination therapy using everolimus (a TOR-inhibitor) and the experimental drug FTY-720 (instead of a calcineurin inhibitor) with basiliximab (an IL-2 inhibitor) induction, in non-human primates showed promising results (four out of five islet recipients were insulin free at six months) (69). Trials examining the efficacy of co-stimulatory blockade (blocking both direct and indirect alloantigen recognition pathways) using humanized anti-CD154 monoclonal antibody initially showed promising results in primates (70). However, the unusual occurrence of thromboembolic events in another trial in kidney transplant recipients led to halting further clinical trials using this agent until this issue can be resolved (71). Other selective co-stimulatory blockers that have been or are being studied are hCTLA4Ig (72) and LEA29Y (73). Similarly, potential tolerance-inducing agents such as the anti-CD52 monoclonal antibody Campath-1H (74) and the anti-CD3 monoclonal antibody OKT3 ala-ala have shown potential benefit in early diabetes prevention trials (75).

Stem cell research has also generated a great deal of interest for its immense potential as a possible unlimited source for transplantable insulin-secreting cells. Several studies have demonstrated that insulin-secretion can be induced from both embryonic stem cells (51; 76) and adult pancreatic ductal stem cells (77-79). While the clinical use of stem cells is not currently feasible, they have great potential to replace the use of cadaveric islets with potentially unlimited non-immunogenic cells (80; 81). Finally, islet encapsulation and xenotransplantation continue to be examined as potential means of overcoming the limited supply of donor islets. Although, the barriers to xenotransplantation are considerable, including immunological incompatibility and the potential transmission of zoonoses to human recipients.