Pancreas preservation in extracellular‐type p38 inhibitor‐containing solution improves islet yield for porcine islet isolation

Abstract

Background For islet transplantation, pancreas preservation and islet isolation activate p38, which is a member of the stress‐activated group of mitogen‐activated protein kinases (MAPKs). In this study, we evaluated an extracellular‐type p38 inhibitor‐containing (EP) solution with University of Wisconsin (UW) solution, the gold standard for organ preservation. The EP solution has high sodium‐low potassium composition with low viscosity compared to UW solution. Moreover, EP solution contains a recently developed p38 inhibitor (11R‐p38I110) from our laboratory. Methods Porcine pancreata were preserved in UW, EP, or EP‐P solution (EP solution without 11R‐p38I110), and then islet isolation was performed. An optimized number (1500 IE) of isolated islets from each group were transplanted into streptozotocin‐induced diabetic mice. Results The islet yield before and after purification was significantly higher in the EP group than in the UW group. The islet yield before and after purification was not significantly different between the EP and EP‐P groups; however, the EP solution prevented a reduction in the number of islets during culture. Western blot analysis showed that p38 activation was attenuated by EP solution. For islet transplantation into streptozotocin‐induced diabetic mice, pancreas preservation in EP solution improved the outcome of islet transplantation. Conclusions Pancreas preservation with EP solution preserved islet function better than with UW solution. The advantages of EP solution over UW solution may include the inhibition of p38 activity as well as the composition of the solution.

Adhesion Characteristics of Human Pancreatic Islets, Duct Epithelial Cells, and Acinar Cells to a Polymer Scaffold

“…Tryptophan ketoglutarate (HTK) solution 37 , ET-Kyoto solution 38 , M-Kyoto solution 39 , and HN-1 solution 40 were later developed in Japan. The comparison and improvement of the composition of these organ preservation solutions have been reported 40 , 41 , 42 , 43 .…”

Clinical Islet Transplantation Covered by Health Insurance in Japan

“…The number of islets from one donor pancreas is usually insufficient to achieve insulin independence [ 1 , 26 , 27 , 28 ], although we achieved it from a single donor in the United States [ 25 ]. The islet isolation procedure destroys the cellular and non-cellular components of the pancreas and the activation of some components, including resident neutrophils, macrophages, and T cells, probably plays an important role in the impairment of islet survival [ 26 , 27 , 28 , 29 , 30 ]. Although the NHI coverage of allogeneic CIT in Japan is a turning point, the donor shortage in Japan is still serious.…”