Select your timezone:

Ethics and Islet transplantation

Saturday October 28, 2023 - 09:35 to 10:35

Room: Indigo A

315.6 Surface modification of Bissulfosuccinimidyl suberate as an encapsulation strategy for islet transplants

Award Winner

Jagan Kalivarathan, United States has been granted the TTS-IPITA Congress Scientific Award

Jagan Kalivarathan, United States

Trainee
Surgery
VCU Health System

Abstract

Surface modification of Bissulfosuccinimidyl suberate as an encapsulation strategy for islet transplants

Jagan Kalivarathan2, Prathab Balaji Saravanan1, Shujauddin Mohammed1, Brian Fuglestad3, Soma Dhakal3, Marlon F Levy2, Mazhar A Kanak1.

1Department of Surgery, Virginia Commonwealth University, Richmond, VA, United States; 2Hume Lee Transplant Center, VCU Health System, Richmond, VA, United States; 3Department of Chemistry, Virginia Commonwealth University, Richmond, VA, United States

Purpose: Early post-transplant inflammation has been a significant factor resulting in the loss of more than 50% of pancreatic islets, affecting long-term islet transplant outcomes. Control of early inflammatory events could improve the efficacy of islet cell transplantation and may enhance the long-term survival of islet grafts. Cell surface modification is an attractive method for masking cell features that may instigate inflammatory cascades. Bissulfosuccinimidyl suberate (BS3) is a homobifunctional crosslinker with NHS ester on each side to bind to amine groups.  Here we have evaluated the surface conjugation potential of BS3 which may be used to immobilize anti-inflammatory compounds onto the surface of the islets for local delivery to the graft microenvironment.

Methods: Human islets (2000IEQ) were surface conjugated with BS3 in different concentrations (0.5 mM, 1 mM, 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 was performed on days 0, 1, 4, and 7 of culture by staining islets with Streptavidin FITC, Hoechst33314, and propidium iodide. The impact of BS3 conjugation on islet function was determined by measuring the oxygen consumption rates (OCR) and glucose-stimulated insulin secretion (GSIS).

Results: The modification of islets with BS3 was found to be exceptionally biocompatible. The viability and functional integrity of islets was 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. Figure 1b shows the surface coverage of islets with BS3 on day 7.

Conclusion: Surface modification of islets with BS3 is a safe and tolerable approach that may be used for localized drug delivery strategies. This approach opens new opportunities for the delivery of bioactive molecules such as anti-inflammatory and immunomodulatory nano-drugs locally in the islet transplant microenvironment.

This work was supported by U.S. Department of Defense (Grant#PR211164).

Organized by

Supported by

Hosted by


IPITA-IXA-CTRMS Joint Congress • San Diego, CA, USA • October 26-29, 2023
© 2024 IPITA-IXA-CTRMS 2023