Since 1999, the combination of steroid-free immunosuppression with newer immunosuppressive agents and the use of at least two separate islet infusions has led to the achievement of insulin independence in the majority of recipients (22). These results are a consistent and marked improvement of islet graft survival and function. The avoidance of long-term glucocorticoids appeared to be especially beneficial because of their well-documented diabetogenic effects, through both direct toxic effects on beta cell function and indirect increases in peripheral and hepatic insulin resistance (23; 24).

Also, improvements in islet isolation techniques, such as the use of the two-layer method of pancreas preservation (25; 26), controlled ductal perfusion (27) and use of low endotoxin-containing collagenase blends (Liberase®, Roche Diagnostics, Indianapolis, IN) for pancreatic digestion have helped improve islet yield, purity and viability. Donor factors that appear to play a role the outcome of clinical islet transplantation are donor age, weight, gender, previous medical history, the presence of hyperglycemia, and the duration of organ ischemia after cardiac arrest (28-30). The technical skills of the local pancreas procurement team can also affect islet yield (29). Furthermore, the process of islet isolation remains time-consuming (6-8 hours per isolation) and labor intensive. Even under ideal circumstances, an estimated yield of only 20-50% of the potential number of pancreatic islets (1-2 million) can be expected. Encouraging results were reported in a series of patients who were transplanted with islets isolated at a remote center (31) indicating that it may be possible and more cost effective to isolate islets at a central (or regional) laboratory for subsequent transplantation at peripheral centers. Continued progress in addressing each of these issues will no doubt contribute to increasing islet yields and further improvement in the viability of islet transplants.