Serine-Protease Inhibition during Islet Isolation Increases Islet Yield from Human Pancreases with Prolonged Ischemia. Transplantation 2001; 72: 565.

ISLET ISOLATION: SIMPLE MODIFICATIONS CAN STILL YIELD BIG IMPROVEMENTS In this issue, J.R.T. Lakey et al. describe increased islet yields from human pancreata achieved by the incorporation of Pefabloc, a serine-protease inhibitor, into the standard Liberase digestion protocol. Improved yield, together with recent advances in transplantation biology, may enable increased numbers of diabetic patients to receive a curative islet graft. Transplantation of insulin-producing tissue as the definitive cure for diabetes was first proposed more than 100 years ago (1). During the last decade, segmental pancreas transplantation has become a standard form of therapy for longstanding diabetes. Success rates have improved steadily and until recently remained far superior to those achieved with isolated islet of Langerhans transplantation (2). Advances in immunosuppression (the “Edmonton protocol”) during the last 2 years, coupled with increased islet graft mass, have now made islet transplantation a realistic therapeutic alternative (3). The reduced antigen load of isolated islets, coupled with the relative simplicity and low morbidity of transcutaneous intrahepatic injection make the procedure increasingly attractive. However, human islet transplantation continues to be hindered by limited availability of islets. The isolation of human islets of Langerhans has always been expensive and labor intensive. The search for ways to improve efficiency and yield has spanned decades. The earliest results with enzymatic digestion of the pancreas (4) led to increasingly pure collagenase preparations and finally to the current standard, Liberase (5). Incubation of minced tissue in enzyme has been replaced by ductal perfusion with the enzyme. Newer media have been used to purify the isolated islets away from unwanted exocrine tissue. Ingenious apparatus has been designed that separates islets from the undigested exocrine mass and then removes them from the enzyme solution (6). The report by Lakey et al. may be the next significant advance in this area. To summarize the results of Lakey et al., the addition of Pefabloc to the isolation protocol doubled the islet yield without detectable detriment to the tissue. In vitro, the islets appeared to be functional. If these results can be confirmed and extended to document function in vivo, they should make it possible to treat many more persons with diabetes. Four years ago the enzyme mixture Liberase was reported to increase markedly the yield of islets (5). Subsequently, this enzyme preparation has become the “gold standard” for islet isolation. Based on the magnitude of the increase in isolated islets presented in the current paper, the addition of Pefabloc could have a similar effect on the islet isolation procedure. Although the authors do not discuss them, their results suggest that Pefabloc may also have other uses, possibly as a preservative for solid organs after harvest and perhaps for pancreata intended for subsequent islet isolation. In any case, this report appears to be good news for diabetic patients awaiting curative transplantation.

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