Cibinetide (ARA 290), the Innate Repair Receptor Ligand, Improves Engraftment in Pancreatic Islet Transplantation by Protecting Islets and Reducing Inflammatory Reactions.
1Department of Transplantation Surgery, CLINTEC, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden
2Araim Pharmaceuticals, Tarrytown, NY
Meeting: 2017 American Transplant Congress
Abstract number: A44
Keywords: Inflammation, Islets
Session Information
Session Name: Poster Session A: Cellular & Bone Marrow Transplantation Session I
Session Type: Poster Session
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 November 22, 2024.« Back to 2017 American Transplant Congress