Long-Term Survival of Neonatal Porcine Islets Without Sertoli Cells in Rabbits

Abstract

Rafael Valdés-González, Ana L. Rodriguez-Ventura, Briceyda González-Ramírez, Benjamín León-Mancilla, Pedro Valencia, María del Carmen García de León, Ruy Pérez-Tamayo

Cell-based therapy is a promising treatment for metabolic disorders such as type-1 diabetes. Transplantation protocols have investigated several anatomical sites for cell implantation; however, some of these procedures, such as intraportal infusion, can cause organ failure or thrombosis secondarily. Bio-artificial organs could be the choice, although concerns still remain. Using a subcutaneous device, we are able to preserve neonatal porcine islets without sertoli cells in healthy New Zealand rabbits. Devices were implanted in the back of the animals underneath the skin, and after 3 months the islets were transplanted. Histology showed the presence of inflammatory cells, predominantly eosinophils; however, insulin- and glucagon-positive cell clusters were identified inside the device at different time points for at least 90 days, and porcine C-peptide was also detected during the follow-up, indicating graft functionality. We have found that our device induces the deposition of a fibrous matrix enriched in blood vessels, which forms a good place for cell grafting, and this model is probably able to induce an immunoprivileged site. Under these conditions, transplanted porcine islet cells have the capability of producing insulin and glucagon for at least three months