Islet transplantation is a method of restoring endogenous insulin secretion in selected patients with type 1 diabetes by transplanting insulin-secreting islet cells isolated from cadaveric donor pancreases, into eligible recipients. Since the introduction of steroid-free immunosuppressive regimens in the late 1990s, the 1-year insulin independence rate of islet recipients, at experienced transplant centers, has risen from less than 10% to approximately 75% (1). These results are a marked improvement in the clinical outcome of islet transplantation. However, a number of issues continue to challenge the wider application of islet transplantation in the treatment of type 1 diabetes. There is still a general requirement for at least two donor pancreases for each islet transplant recipient. Also the necessity for toxic immunosuppressive therapy and a gradual decline in insulin independence rates over time continue to make this procedure unsuitable for the majority of people with type 1 diabetes. Nevertheless, the recent improvement in islet engraftment has stimulated further investigation of beta cell replacement as a potential therapy for type 1 diabetes.

Experimental isolation of rodent islets began in the 1960s to characterize islet morphology and cellular physiology (2). By the end of the decade the mass isolation of rodent islets was readily achievable. However, the large size (70g) and fibrous quality of the human pancreas makes human islet isolation more difficult. By the 1980s, successful islet isolation and transplantation was achieved in dogs and pigs (3-7).

In 1988 Ricordi et al introduced a semi-automated method of isolating human islets using collagenase digestion and mechanical agitation inside a stainless-steel chamber containing glass (or steel) marbles, and a 500 μm mesh screen to separate insulin-secreting islets from pancreatic stromal tissue (8). The liberated islets were sampled frequently to avoid over-digestion and fragmentation. This process has now become the standard method for the isolation of human islets for transplantation. The adaptation of a COBE cell separation technique using Ficoll density gradients has produced greater purity of islets preparations, although this technique tends to reduce the overall islet yield (9).

In the early 1990s, a number of human islet transplant trials were attempted, and despite achieving insulin independence in a few recipients, the results were generally disappointing (10-15). By 1999, the International Islet Transplant Registry recorded a total of 447 human islet allografts performed worldwide (16). The results showed that insulin independence was achieved only in exceptional cases, when more than 6000 Islets/kg had been infused and when the cold storage time of the donated pancreas was less than 8 hours (17). Although 28% of cases showed detectable serum C-peptide levels after one year (18), the overall 1-year insulin independence rate was only 8% (16). By the late 1990s, steroid-free immunosuppressive protocols introduced for islet-after-kidney transplants, reported early insulin independence rates of up to 66% although this was not generally sustained for long periods (19; 20). Soon, progress in islet isolation techniques and the use of newer immunosuppressive agents would lead to a dramatic and sustained improvement in islet graft function (21).