Increased islet viability by addition of beraprost sodium to collagenase solution.

Summary: The digestion of pancreatic tissue with collagenase is an essential part of the islet isolation procedure. However, the process exposes islets to various types of harmful factors, including collagenase contaminants, enzymes released from the acinar cells, warm ischemia, and mechanical agitation. Nitrogen oxide production and cytokine release may also contribute to islet cell damage. Protection of islets from such damage would improve the islet yield, survival, and function. Beraprost sodium (BPS) is a prostaglandin I2 analogue, is stable in aqueous solution, and has a cytoprotective effect on various types of cells. BPS has been shown to improve the yield and function of cryopreserved and/or cultured islets. These findings prompted us to examine its cytoprotective effect on islets during the islet isolation process. Canine islets were isolated by means of a two-step digestion method and purified on Euro-Ficoll density gradient solutions (the procedure used for human islets). BPS at a concentration of 100 n M was added to the collagenase solution. After purification, the islet yield was 434,561 ± 35,691 islet number expressed as 150 μm equivalent size (IEQ)/pancreas or 8,799 ± 345 IEQ/g of pancreas in the BPS group and 349,987 ± 52,887 IEQ/pancreas or 7,998 ± 1610 IEQ/g of pancreas in the control group (n = 8, each). The percent viability was 88.5 ± 0.7% in the BPS group and 82.0 ± 0.9% in the control group (P 6). These results indicate that the addition of BPS to the collagenase solution increases the recovery of viable islets, and improves β cell function.