1504-P: AdoShell, a Nonfibrotic Encapsulation System for Human Islets Transplantation, Shows Promising Results for Clinical Application as a Cure for People with Type 1 Diabetes

AdoShell® is an easily implantable and fully retrievable scaffold for islet transplantation aiming to cure diabetes by cell therapy without requiring immunosuppression. It is based on a permselective hydrogel film allowing insulin diffusion while preventing immune cell invasion. Allogenic transplant of rat islets in immunocompetent diabetic rats has already demonstrated encapsulated islets survival, insulin secretion, and glycemic regulation. Compatibility with human islets, good local tolerance, and scalability to deliver a therapeutic dose were studied to meet requirements for a first in human. In vitro, AdoShell® Human Islets has shown gluco-responsive insulin secretion up to 7 months. AdoShell® tolerance was evaluated in the intraperitoneal site of immunocompetent rodent species, with or without human islets: AdoShell was well tolerated and did not trigger inflammatory reaction or fibrosis. AdoShell® Human Islets in vivo functionality was evaluated in immunodeficient mice. Human C-peptide secretion increased during the first two weeks to reach an average of 446 ± 130 pM/day and was maintained until explantation on day 62 (n=4 mice). These results were confirmed in a second study. In vitro analysis of the explants by static GSIS (n=6 explants) showed 21% ± 15 of preimplantation insulin secretion levels, while the mean secretion index was maintained. Therefore, AdoShell favors human islets in vivo functionality. A human sized AdoShell® with the potential to deliver a therapeutic islet dose was successfully manufactured and implanted by laparoscopy in domestic pig. AdoShell® Islets is suitable for human islets delivery showing good local tolerance without fibrosis and sustained islet functionality.