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Updated: May 18, 2026
Transplantation of Pancreatic Islets Into the Kidney Capsule of Diabetic Mice
Published on: October 31, 2007
CXCR1/2 inhibition enhances pancreatic islet survival after transplantation
Antonio Citro1, Elisa Cantarelli, Paola Maffi
1San Raffaele Diabetes Research Institute (HSR-DRI), Milan, Italy.
Abstract:
Although long considered a promising treatment option for type 1 diabetes, pancreatic islet cell transformation has been hindered by immune system rejection of engrafted tissue. The identification of pathways that regulate post-transplant detrimental inflammatory events would improve management and outcome of transplanted patients. Here, we found that CXCR1/2 chemokine receptors and their ligands are crucial negative determinants for islet survival after transplantation. Pancreatic islets released abundant CXCR1/2 ligands (CXCL1 and CXCL8). Accordingly, intrahepatic CXCL1 and circulating CXCL1 and CXCL8 were strongly induced shortly after islet infusion. Genetic and pharmacological blockade of the CXCL1-CXCR1/2 axis in mice improved intrahepatic islet engraftment and reduced intrahepatic recruitment of polymorphonuclear leukocytes and NKT cells after islet infusion. In humans, the CXCR1/2 allosteric inhibitor reparixin improved outcome in a phase 2 randomized, open-label pilot study with a single infusion of allogeneic islets. These findings indicate that the CXCR1/2-mediated pathway is a regulator of islet damage and should be a target for intervention to improve the efficacy of transplantation.
Insights
Targeting the CXCR1/2 pathway improves pancreatic islet transplantation outcomes. Blocking this pathway reduces immune rejection and enhances islet survival, offering new hope for type 1 diabetes treatment.
Area of Science:
- Immunology
- Endocrinology
- Transplantation Biology
Background:
- Pancreatic islet transplantation is a promising therapy for type 1 diabetes but is limited by immune rejection.
- Understanding inflammatory pathways post-transplant is crucial for improving engraftment and survival.
Purpose of the Study:
- To investigate the role of CXCR1/2 chemokine receptors and their ligands in islet transplantation outcomes.
- To identify therapeutic targets for mitigating detrimental inflammatory responses after islet infusion.
Main Methods:
- Utilized genetic and pharmacological blockade of the CXCL1-CXCR1/2 axis in mouse models.
- Administered reparixin, a CXCR1/2 inhibitor, in a human phase 2 clinical trial for islet transplantation.
Main Results:
- Blockade of the CXCL1-CXCR1/2 axis significantly improved intrahepatic islet engraftment in mice.
- Reduced recruitment of polymorphonuclear leukocytes and NKT cells was observed post-infusion.
- Reparixin treatment improved outcomes in a pilot study of allogeneic islet transplantation in humans.
Conclusions:
- The CXCR1/2-mediated pathway is a critical negative regulator of islet survival post-transplantation.
- Targeting CXCR1/2 represents a promising therapeutic strategy to enhance islet transplantation efficacy.