Abstract 1032: Development Of A Bio-hybrid Endovascular Stent-graft That Enables Immunosuppression Free Islet Cell Transplantation

Abstract

Introduction: Islet cell transplantation has had limited clinical success freeing type 1 diabetics from exogenous insulin. Currently, islet cell transplants are performed via infusion of islet cells into the recipient's portal vein. Approximately 60% of transplanted cells die within 3 days of transplantation due to ischemic injury. Significant immunosuppression is needed to avoid rejection but is also toxic to islet cells. We have developed a novel endovascular biologic stent-graft that provides cellular immunoisolation while preventing ischemic injury through endovascular deployment (Fig 1). Hypothesis: We hypothesize islet cells seeded within the semipermeable biohybrid endovascular graft will survive and secrete insulin in an in-vitro model of perfusion. Methods: The semipermeable cell chamber was made from ePTFE with a pore size of 0.22 um, and was seeded with islet cells harvested from BALB/c mice. A normothermic machine perfusion circuit was used to model intravascular deployment. Devices were exposed to varying glucose concentrations and insulin was detected by ELISA. Results: There were significantly higher levels of insulin secretion after exposure to high vs low glucose media (p = 0.005). At hour 3 of low glucose (2.8 mM), the average insulin concentration was 76 ± 14 mIU/ml, and at hour 3 of high glucose (28 mM), the average insulin concentration was 134 ± 30 mIU/ml (Fig 2). The rate of insulin secretion was significantly higher in high vs low glucose conditions (6759 ± 503 mIU/h vs. 5344 ± 144 mIU/hr, p = 0.008). Conclusions: The endovascular biohybrid device enables islet cell function and survival. In-vivo studies are needed to study the immune interactions.