Porcine Islets Engineered to Display SA-FasL Protein on Their Surface Induce Tolerance in Mice Following Transplantation into the Liver or Under the Kidney Capsule.
1Institute for Cellular Therapeutics and Department of Microbiology and Immunology, University of Louisville, Louisville, KY
2Schulze Diabetes Institute and Department of Surgery, University of Minnesota, Minneapolis, MN.
Meeting: 2016 American Transplant Congress
Abstract number: 364
Keywords: Engraftment, Fas ligand, Immunosuppression, Xenotransplantation
Session Information
Session Name: Concurrent Session: Xenotransplantation: Animal Models
Session Type: Concurrent Session
Date: Monday, June 13, 2016
Session Time: 4:30pm-6:00pm
Presentation Time: 5:18pm-5:30pm
Location: Room 102
Introduction: We have recently demonstrated that allogeneic islets engineered to transiently display on their surface a novel form of FasL protein chimeric with streptavidin (SA-FasL) induce tolerance in allogeneic mouse models. In this study, we tested the efficacy of this approach in inducing tolerance to porcine islets transplanted into mice using two different transplant sites; subrenal and intraportal.
Methods: Porcine islets were modified with 5 [micro]M biotin and engineered with SA-FasL protein (~200 ng/1000 islets). SA-FasL-engineered islets were transplanted under the kidney capsule (~2000 islets/transplant) or intraportally (2,500 islets/transplant) in streptozotocin diabetic C57BL/6 mice under a transient cover (20 days) of rapamycin. Unmodified pancreatic islets with rapamycin treatment served as controls.
Results: Porcine islets were effectively engineered with SA-FasL protein without a detrimental effect on their viability and function. SA-FasL-engineered islets induced apoptosis in responding mouse T cells in in vitro co-culture experiments. All control grafts with transient rapamycin treatment were rejected within 30 days post-transplantation. In marked contrast, all SA-FasL-engineered porcine grafts showed prolongation and ~60% of intraportal (n=37) and ~80% of subrenal (n=22) grafts survived for a 300-day observation period. Intraperitoneal glucose tolerance test demonstrated normal function of long-term islets, with the subrenal model performing better than the intraportal model. There was no detectable signs of acute or chronic toxicity of the procedure. The long-term euglycemia was due to the transplanted porcine islets as the surgical removal of the grafts resulted in prompt hyperglycemia.
Conclusion: SA-FasL as an immunomodulatory molecule is effective in inducing tolerance to porcine islet grafts transplanted subrenally as a standard site in rodents and intraportally as a clinically applicable yet immunologically more challenging site.
CITATION INFORMATION: Zhao H, Woodward K, Shirwan H, Graham M, Hering B, Yolcu E. Porcine Islets Engineered to Display SA-FasL Protein on Their Surface Induce Tolerance in Mice Following Transplantation into the Liver or Under the Kidney Capsule. Am J Transplant. 2016;16 (suppl 3).
To cite this abstract in AMA style:
Zhao H, Woodward K, Shirwan H, Graham M, Hering B, Yolcu E. Porcine Islets Engineered to Display SA-FasL Protein on Their Surface Induce Tolerance in Mice Following Transplantation into the Liver or Under the Kidney Capsule. [abstract]. Am J Transplant. 2016; 16 (suppl 3). https://atcmeetingabstracts.com/abstract/porcine-islets-engineered-to-display-sa-fasl-protein-on-their-surface-induce-tolerance-in-mice-following-transplantation-into-the-liver-or-under-the-kidney-capsule/. Accessed May 2, 2025.« Back to 2016 American Transplant Congress