TY - JOUR
T1 - Preservation of pancreas in the University of Wisconsin solution supplemented with AP39 reduces reactive oxygen species production and improves islet graft function
AU - Nishime, Kai
AU - Miyagi-Shiohira, Chika
AU - Kuwae, Kazuho
AU - Tamaki, Yoshihito
AU - Yonaha, Tasuku
AU - Sakai-Yonaha, Mayuko
AU - Saitoh, Issei
AU - Watanabe, Masami
AU - Noguchi, Hirofumi
N1 - Funding Information:
We thank Naomi Kakazu (University of the Ryukyus) for the office processing and Yuki Kawahira and Ikue Honda (University of the Ryukyus) for technical support. This work was supported in part by JSPS KAKENHI Grant Numbers JP20H03745 and JP19K09051, and the Okinawa Science and Technology Innovation System Construction Project.
Funding Information:
We thank Naomi Kakazu (University of the Ryukyus) for the office processing and Yuki Kawahira and Ikue Honda (University of the Ryukyus) for technical support. This work was supported in part by JSPS KAKENHI Grant Numbers JP20H03745 and JP19K09051, and the Okinawa Science and Technology Innovation System Construction Project.
Publisher Copyright:
© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons
PY - 2021/8
Y1 - 2021/8
N2 - Ischemia-reperfusion injury (IRI) results in increased rates of delayed graft function and early graft loss. It has recently been reported that hydrogen sulfide (H2S) protects organ grafts against prolonged IRI. Here, we investigated whether the preservation of pancreas in University of Wisconsin (UW) solution supplemented with AP39, which is a mitochondrial-targeted H2S donor, protected pancreatic islets against IRI and improved islet function. Porcine pancreata were preserved in the UW solution with AP39 (UW + AP39) or the vehicle (UW) for 18 h, followed by islet isolation. The islet yields before and after purification were significantly higher in the UW + AP39 group than in the UW group. The islets isolated from the pancreas preserved in UW + AP39 exhibited significantly decreased levels of reactive oxygen species (ROS) production and a significantly increased mitochondrial membrane potential as compared to the islets isolated from the pancreas preserved in the vehicle. We found that the pancreas preserved in UW + AP39 improved the outcome of islet transplantation in streptozotocin-induced diabetic mice. These results suggest that the preservation of pancreas in UW + AP39 protects the islet grafts against IRI and could thus serve as a novel clinical strategy for improving islet transplantation outcomes.
AB - Ischemia-reperfusion injury (IRI) results in increased rates of delayed graft function and early graft loss. It has recently been reported that hydrogen sulfide (H2S) protects organ grafts against prolonged IRI. Here, we investigated whether the preservation of pancreas in University of Wisconsin (UW) solution supplemented with AP39, which is a mitochondrial-targeted H2S donor, protected pancreatic islets against IRI and improved islet function. Porcine pancreata were preserved in the UW solution with AP39 (UW + AP39) or the vehicle (UW) for 18 h, followed by islet isolation. The islet yields before and after purification were significantly higher in the UW + AP39 group than in the UW group. The islets isolated from the pancreas preserved in UW + AP39 exhibited significantly decreased levels of reactive oxygen species (ROS) production and a significantly increased mitochondrial membrane potential as compared to the islets isolated from the pancreas preserved in the vehicle. We found that the pancreas preserved in UW + AP39 improved the outcome of islet transplantation in streptozotocin-induced diabetic mice. These results suggest that the preservation of pancreas in UW + AP39 protects the islet grafts against IRI and could thus serve as a novel clinical strategy for improving islet transplantation outcomes.
KW - basic (laboratory) research / science
KW - ischemia reperfusion injury (IRI)
KW - islet isolation
KW - islet transplantation
KW - organ perfusion and preservation
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U2 - 10.1111/ajt.16401
DO - 10.1111/ajt.16401
M3 - Article
C2 - 33210816
AN - SCOPUS:85097992111
VL - 21
SP - 2698
EP - 2708
JO - American Journal of Transplantation
JF - American Journal of Transplantation
SN - 1600-6135
IS - 8
ER -