DIACEST Islet Cell Capsules for Immunoprotection, MR Detection, and pH Sensing

Hugo W. Moser Res Inst Kennedy Krieger, Baltimore MD

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Abstract

DESCRIPTION (provided by applicant): 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 involves 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: 1) detection, 2) discrimination between encapsulated islet and mesynchymal stem cells and 3) remote sensing of the pH of the environment. The source of the CEST contrast will be 6-24 amino acid 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/ mesenchymal cells through firefly luciferase expression. PUBLIC HEALTH RELEVANCE: Islet transplantation (ITx) has received considerable attention in recent years for treatment of Type 1 Diabetes Melitus (T1DM). This proposal is focused on the production of immunoprotective islet cell capsules which are appropriate for treatment and allow MR monitoring of the pH these islets using biodegradable CEST contrast agents.