2086-LB: Islet Surface Modification with Bissulfosuccinimidyl Suberate Prevents the Instant Blood-Mediated Inflammatory Reaction—A Novel Approach

Introduction and Objectives: In pancreatic islet cell transplantation, the early graft loss is due to the instant blood-mediated reaction (IBMIR). Control of early inflammatory events could improve the efficacy of islet cell transplantation and may enhance the long-term function of transplanted islets. Nanoencapsulation of islets is an attractive method for masking cell features that can trigger inflammatory cascades. Bissulfosuccinimidyl suberate (BS³) is a homobifunctional crosslinker with NHS ester on each side to bind to amine groups. Herein, we investigated the effects of BS³-modified human islets in terms of viability, function, longevity of modification, and inflammatory properties.

Methods: The surface of the human islets was modified with BS³ in different concentrations (0.5, 1, and 5 mM). Visual coverage and efficiency of surface conjugation were determined by incorporating an Amine-PEG-Biotin conjugate. Surface-conjugated islets were then cultured for 7 days. Visualization of conjugation and viability determination was performed days 0, 1, 4, and 7 of culture. The impact of BS³ conjugation on islet function was determined by measuring the oxygen consumption rates and glucose-stimulated insulin secretion.

Results: BS³ modification was found to be exceptionally biocompatible. The viability and functional integrity of islets were not altered at 0.5 mM and 1 mM BS³, but viability showed a mild decline at 5 mM BS3. However, improved conjugation of the islet surface and good coverage were noted in the 5 mM BS³ group. The surface modification was maintained for all 7 days tested with minimal loss of coverage. The markers of inflammation were examined using qPCR analysis. BS³ treated group showed higher inhibition of all pro-inflammatory genes under strong cytokine cocktail exposure.

Conclusion: Surface modification of islets with BS³ is a safe and tolerable approach that may be used for localized drug delivery strategies.