Date: Saturday, April 29, 2017
Session Time: 5:30pm-7:30pm
Presentation Time: 5:30pm-7:30pm
Location: Hall D1
Purpose. Cibinetide, an innate repair receptor ligand, exerts anti-inflammatory, anti-apoptotic, and cytoprotective effects. We have shown that cibinetide protected mouse pancreatic islets from cytokine-induced damage and improved engraftment of islet following syngeneic islet transplantation (ITx). We further investigated the efficacy of cibinetide in allogeneic ITx and examined a graft-protective effect on human pancreatic islets.
Methods. Human pancreatic islets were cultured together with pro-inflammatory cytokines in the presence or absence of cibinetide. Human islets were transplanted into the liver of athymic mice via the portal vein. BALB/c (H-2d) mice islets were transplanted into streptozotocin-induced diabetic C57BL/6 (H-2b) mice. Recipients were given cibinetide (120 [micro]g/kg) intraperitoneally just before, immediately after, 6, and 24 hours after ITx.
Results. During the exposure to pro-inflammatory cytokines, the addition of cibinetide maintained the ATP level and suppressed caspase 3/7 activity in the human islets. Cibinetide treatment improved engraftment of human islets, indicated by higher human insulin amount in the recipient liver at 6 days after ITx (Fig.A). The treatment with cibinetide reduced inflammatory responses, shown by significantly low mRNA expression of IL-1 and IL-6 in the recipient liver harvested at 16 hours after ITx, and prolonged islet allograft survival time compared to those of control group animals (19.3 vs. 1.4 days; p<0.01, Fig.B). The frequency of allo-reactive IFN-γ producing precursors in the spleen was significantly lower in the cibinetide treated animals at 5 days after ITx. Conclusion. Cibinetide protects human islets from inflammatory damage. Suppression of initial inflammatory reactions by cibinetide protects islets, and also reduces subsequent allo-immune responses. Use of cibinetide in the peri-implant period might be beneficial for ITx.
CITATION INFORMATION: Watanabe M, Han Yao M, Zemack H, Ericzon B.-G, Cerami A, Brines M, Lundgren T, Kumagai-Braesch M. Cibinetide (ARA 290), the Innate Repair Receptor Ligand, Improves Engraftment in Pancreatic Islet Transplantation by Protecting Islets and Reducing Inflammatory Reactions. Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:Watanabe M, Yao MHan, Zemack H, Ericzon B-G, Cerami A, Brines M, Lundgren T, Kumagai-Braesch M. Cibinetide (ARA 290), the Innate Repair Receptor Ligand, Improves Engraftment in Pancreatic Islet Transplantation by Protecting Islets and Reducing Inflammatory Reactions. [abstract]. Am J Transplant. 2017; 17 (suppl 3). https://atcmeetingabstracts.com/abstract/cibinetide-ara-290-the-innate-repair-receptor-ligand-improves-engraftment-in-pancreatic-islet-transplantation-by-protecting-islets-and-reducing-inflammatory-reactions/. Accessed July 8, 2020.
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