Pancreas Preservation with a Neutrophil Elastase Inhibitor, Alvelestat, Contributes to Improvement of Porcine Islet Isolation and Transplantation

by Selleckchem | Sep 28 2023

For pancreatic islet transplantation, pancreas procurement, preservation, and islet isolation destroy cellular and non-cellular components and activate components such as resident neutrophils, which play an important role in the impairment of islet survival. It has been reported that inhibitors of neutrophil elastase (NE), such as sivelestat and α1-antitrypsin, could contribute to improvement of islet isolation and transplantation. In this study, we investigated whether pancreatic preservation with alvelestat, a novel NE inhibitor, improves porcine islet yield and function. Porcine pancreata were preserved with or without 5 μM alvelestat for 18 h, and islet isolation was performed. The islet yields before and after purification were significantly higher in the alvelestat (+) group than in the alvelestat (-) group. After islet transplantation into streptozotocin-induced diabetic mice, blood glucose levels reached the normoglycemic range in 55% and 5% of diabetic mice in the alvelestat (+) and alvelestat (-) groups, respectively. These results suggest that pancreas preservation with alvelestat improves islet yield and graft function and could thus serve as a novel clinical strategy for improving the outcome of islet transplantation.

Comments:

The study you mentioned investigated the potential benefits of using alvelestat, a novel neutrophil elastase (NE) inhibitor, for pancreatic islet transplantation. Pancreatic islet transplantation involves the procurement, preservation, and isolation of islets from the pancreas, which can cause damage to both cellular and non-cellular components, as well as activate resident neutrophils. These factors can negatively impact the survival and function of transplanted islets.

In the study, porcine pancreata were preserved with or without the addition of 5 μM alvelestat for 18 hours, and then the islets were isolated. The researchers found that the islet yields, both before and after purification, were significantly higher in the alvelestat (+) group compared to the alvelestat (-) group. This suggests that alvelestat improved the overall yield of viable islets during the isolation process.

Furthermore, the researchers conducted islet transplantation experiments in diabetic mice induced with streptozotocin. They found that blood glucose levels reached the normal range in 55% of the mice transplanted with islets preserved with alvelestat, while only 5% of the mice transplanted with islets preserved without alvelestat achieved normoglycemia. This indicates that alvelestat-preserved islets had better graft function and improved the outcome of islet transplantation.

Based on these findings, the study suggests that pancreatic preservation with alvelestat could be a promising clinical strategy to enhance the success of islet transplantation. By inhibiting neutrophil elastase, alvelestat may help reduce damage to islets during the isolation and transplantation process, leading to improved islet yield and function. However, further research and clinical trials would be necessary to confirm these results and evaluate the safety and effectiveness of alvelestat in human islet transplantation.