Improvement of Metabolic Function after Intra-Portal Allogeneic Islet Transplantation by Induction Treatment of the Non-Hematopoetic Erytropoetin Analogue Cibinetide in a Mouse Model
1Department of Transplantation Surgery, Karolinska University Hospital, Stockholm, Sweden
2Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Meeting: 2018 American Transplant Congress
Abstract number: 18
Keywords: Islets
Session Information
Session Name: Concurrent Session: Islet Cell and Cell Transplantation
Session Type: Concurrent Session
Date: Sunday, June 3, 2018
Session Time: 2:30pm-4:00pm
Presentation Time: 3:42pm-3:54pm
Location: Room 2AB
Introduction
Recently, we have demonstrated that cibinetide, a non-hematopoetic erytropoetin analogue, protected pancreatic islets from cytokine-induced damage and apoptosis and ameliorated the early inflammatory response following PITx. In this study, we investigate the effect of cibinetide on adaptive immunity with focus on its efficacy as induction treatment and dendrtitic cell development in allogenic PITx.
Methods
Pancreatic islets (450) from BALB/c mice were transplanted into the recipient livers of diabetic C57B/6 mice via the portal vein, followed by treatment: (1) cibinetide (120 [micro]g/kg) intraperitoneally (IP), just before and at 0, 6 hrs after PITx, and once daily thereafter until day 14, or with (2) vehicle (PBS) as the control, (3) Tacrolimus (0.4 mg/kg) IP daily from day 4 until day 14 or (4) combination treatment of cibinetide and tacrolimus. Non-fasting blood glucose were monitored as indication of graft function. Mouse bone marrow derived dendritic cells (DC) were differentiated with mouse GM-CSF and IL-4 with or without cibinetide (100 nM). DC maturation was compared by examining IL-12 production, MHC class II expression on CD11c+ DCs.
Results
Cibinetide treated mice had an median survival time (MST) 13 days vs 10 days in the control group. The tacrolimus treated mice had an MST of 28,5 days, while in the combination treatment group, 4/5 mice maintained euglycemic even after day 50. 
Cibinetide treatment partially reduces DC maturation in vitro, shown by lower expression of MHC ClassII antigens on DC (approximately 10% lower mean fluorescent intensity, p<0.05) and lower production of IL-12 (920±25 vs 750±22 ng/ml, p<0.05).
Conclusion
Combination therapy with cibinetide and low dose tacrolimus could be useful option to improve allograft survival. Cibinetide treatment reduced DC activation, which can delay the onset of adaptive immune responses.
CITATION INFORMATION: Yao M., Watanabe M., Sun S., Ericzon B., Lundgren T., Kumagai-Braesch M. Improvement of Metabolic Function after Intra-Portal Allogeneic Islet Transplantation by Induction Treatment of the Non-Hematopoetic Erytropoetin Analogue Cibinetide in a Mouse Model Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:
Yao M, Watanabe M, Sun S, Ericzon B, Lundgren T, Kumagai-Braesch M. Improvement of Metabolic Function after Intra-Portal Allogeneic Islet Transplantation by Induction Treatment of the Non-Hematopoetic Erytropoetin Analogue Cibinetide in a Mouse Model [abstract]. https://atcmeetingabstracts.com/abstract/improvement-of-metabolic-function-after-intra-portal-allogeneic-islet-transplantation-by-induction-treatment-of-the-non-hematopoetic-erytropoetin-analogue-cibinetide-in-a-mouse-model/. Accessed November 23, 2024.« Back to 2018 American Transplant Congress