Improved recovery of cryopreserved canine islets by use of beraprost sodium

Cryopreservation of pancreatic islets provides many advantages for clinical transplantation. Unfortunately, the freezing and thawing processes lead to a significant loss of islets. In this study, an attempt was made to increa se the yield and viability of islets after cryopreservation and thawing. By using canine islets, we evaluated whether beraprost sodium (BPS), a stable prostacyclin analog, protects islets during the freeze-thaw processes and improves the recovery of frozen-thawed islets. Canine islets were frozen an d thawed by the procedures used routinely for storage of human islets. In t his study, we deliberately used islets of lower purity (60 +/- 3.6%), which is undesirable for cryopreservation. The recovery of viable islets after t hawing is poorer with islets of lower purity than with highly purified isle ts. BPS was added to both the cryopreservation solutions containing dimethy l sulfoxide (DMSO) and the thawing solution containing sucrose. After thawi ng, the islet recovery (islet number after thawing divided by islet number before freezing) was 71.1 +/- 12.7% with 1 nM BPS, 77.8 +/- 5.6% with 10 nM BPS, 79.3 +/- 6.7% with 100 nM BPS, and 69.2 +/- 7.2% in control preparati ons without BPS. Islet viability assessed by supravital staining was 57.5 /- 5.6%, 64.7 +/- 7.0%, 67.5 +/- 6.5%, and 57.7 +/- 4.9% with 1 nM, 10 nM, and 100 nM BPS and controls, respectively. Both islet recovery and viabilit y were significantly better with 10 nM and 100 nM BPS than with the control s (p < 0.03). After 3 days in culture, islet numbers in the 10 nM and 100 n M BPS groups were significantly higher and showed better insulin-release re sponses than those from the 1 nM BPS and control groups. Histologically, is let structure was well preserved in the 10 nM and 100 nM BPS groups, wherea s many islets of the control group were smaller and fragmented. Electron mi croscopic examination revealed that 10 nM and 100 nM BPS preserved the micr ostructure of islet cells, and signs of apoptosis or necrosis were rare. It was concluded that BPS improved the recovery and viability of canine islet s after cryopreservation and thawing. BPS would be a useful agent for impro ving the recovery of cryopreserved human islets for clinical transplantatio n.