Th187 - The NOD Disease Improved by Grafting the Islets Labeled with Nanoparticles to Facilitate the Immunosuppression and Graft Tracking

Jyuhn-Huarng Juang – Division of Endocrinology and Metabolism, Department of Internal Medicine and Center for Tissue Engineering – Chang Gung Memorial Hospital; Jiun-Jie Wang – Department of Medical Imaging and Radiological Sciences – Chang Gung University; Shu-Ting Wu – Department of Medical Biotechnology and Laboratory Science – Chang Gung University; Sung-Han Lin – Department of Medical Imaging and Radiological Sciences – Chang Gung University; Chao-Lin Liu – Department of Chemical Engineering – Ming Chi University of Technology

Abstract Text: Islet transplantation has been proven to be effective in treating patients with insulin-dependent diabetes mellitus (IDDM). However, suppression of immune rejection and graft tracking appears to be the primary concerns. Recent works done by others and our groups suggest a non-invasive and quantitative in vivo imaging system of superparamagnetic iron oxide nanoparticles (SPION) and magnetic resonance (MR) imaging for clinicians to monitor grafted islets in a real-time manner. To enhance the survival of grafted islets, here we have further developed the above contrast agent that is equipped with immune modulators including IL-10 and PD-L1 to avoid rejection and autoreactive immunity. The results have demonstrated that the application of such specific nanoparticles has led to the success of allotransplantation by extending the survival of transplanted islets. Moreover, the elevated level of blood sugar in IDDM, which results from the damage of islets by the autoimmune T cells, was reduced in non-obese diabetes (NOD) mice. Also, we have shown that the activating T cells could be induced to undergo apoptosis by PD-1 when interacting with the specific ligand, PD-L1. In addition, the agent could enable graft imaging by both IVIS and MRI if the agent was equipped with a reporter, luciferase. In summary, these results concluded that the grafted islets labeled with the multi-functional nanoparticles facilitated immunosuppression and graft tracking for allotransplantation as well as autoimmune diabetes in NOD mice.