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OIACEST Islet Cell Capsules for Immunoprotection, MR Detection, and pH Sending
Good glycemic control is critical in reducing the end-stage complications of Type I Diabetes Mellitus (TIDM) and, for this reason, islet transplantation (ITx) has received considerable attention in recent years, with one of the complications in the treatment involving finding an effective means to prevent rejection. Immuno-isolation of islets provides a means to reduce or avoid immunosuppressive therapy altogether.
In the most commonly used method of immuno-isolation, microencapsulation, individual islets are surrounded with thin alginate membranes that are permeable to insulin and metabolites, but are impermeable to native antibodies. However, the viability and in particular the insulin secretion of these islets are critical for the success of the therapy, and would be important to monitor for refinement of the treatment protocol.
This proposal is focused on the production of micron-sized CEST MR detectable alginate capsules containing both islet and mesenchymal stem cells which are appropriate for the treatment of T1DM. These capsules will have CEST MR contrast agents built into the capsule to allow:
- Discrimination between encapsulated islet and mesynchymal stem cells
- Remote sensing of the pH of the environment
The source of the CEST contrast will be 6-24 amino acide long peptides and CEST liposomes embedded within the alginate. We will perform pre-clinical studies using a nude-based mouse model of diabetes to allow monitoring of the status of encapsulated islets and mesenchymal cells through firefly luciferase expression.