Therapeutic Potential of the Transplanted Islets, Labelled by the Multi-Functional Mr Contrast Agents Facilitating the Graft Tracking and Immunomudulation for Autoimmune Diabetes in Nod Mice

Cell transplantation such as bone marrow, stem cells and islets are believed to be effective in treating diseases. For example, islet transplantation has been proved as an efficient treatment for patients with insulin-dependent diabetes mellitus (IDDM). However, graft tracking and suppression of immune rejection are the two primary issues. To achieve the first goal, a non-invasive and quantitative in vivo imaging system would be a very helpful tool for clinicians to monitor graft survival. Recent works done by our group and others suggest the combination of superparamagnetic iron oxide nanoparticles (SPION) together with magnetic resonance (MR) imaging can be used for in-vivo imaging of transplanted islet in real-time manner. To achieve the second goal of enhancing survival of grafted islets, we have further developed a contrast agent that is equipped with immune-modulators including IL-10 to avoid rejection immunity. In fact, the application of such specific agent has led to the success of allo-transplantation. Also, we have demonstrated that the agent could enable the graft imaging by both IVIS and MRI if the agent was also equipped with the reporter luciferase, indicating multi functions of the agent. In addition, IDDM is resulted from the damage of islet by the autoimmune T cells. We and others have demonstrated that the activating T cells could be induced undergo apoptosis by PD-1 when interacting with the specific ligands such as PD-L1. Therefore, the non-obese diabetic (NOD) mice which spontaneously develop autoimmune diabetes will be utilized in this study. The therapeutic potential will be evaluated, of the grafted islets labelled with the multi-functional contrast agent facilitating the graft tracking and immunosuppression for allotransplantation as well as autoimmune diabetes in NOD mice. Four specific aims are as followed. 1. IVIS and MRI tracking of grafted islets labelled with the multi-functional contrast agent in NOD mice 2. Assessment of the therapeutic effects of grafted islets labelled with the multi-functional contrast agent on diabetes and allotransplantation in NOD mice 3. Identification of the beneficial effects of PD-1/PD-L1 on autoimmune responses in NOD mice 4. Evaluation of the therapeutic potential of grafted islets labelled with the multi-functional contrast agent combined with PD-1 blocker on diabetes, allotransplantation and autoimmune responses in NOD mice The results generated in this current 3-year proposal will not only demonstrate a novel therapeutic strategy for IDDM but also suggest a useful tool for monitoring and enhancing the survival of graft in cell and tissue transplantation.

Project ID:PC10601-0108
External Project ID:MOST104-2320-B182-021-MY3