Innovative Strategies for Type 1 Diabetes treatment

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Ma, Mingyang, Cell Biology - School of Medicine, University of Virginia
Brayman, Kenneth, MD-SURG Transplant Surgery, University of Virginia
Laurie, Gordon, MD-CELL Cell Biology, University of Virginia

Type 1 Diabetes (T1D) presents significant therapeutic challenges due to its autoimmune nature and the critical need for functional pancreatic islet cells. This dissertation utilized in vitro and in vivo models to investigate integrated therapeutic strategies for T1D treatment, focusing on N-104 peptide for immunomodulation and Microporous Annealed Particle (MAP) scaffolds for enhanced islet cell delivery and function. I proved that N-104 signifi-cantly enhances the functionality and survival of islet cells in both mouse and human mod-els, which is vital for the success of islet transplantation. More importantly, N-104 dis-played a pronounced immunomodulatory effect, reducing T-cell-mediated autoimmune re-sponses, a key characteristic of T1D pathology. In Non-obese Diabetic (NOD) mouse models, the systemic administration of N-104 not only prevented the onset of T1D but also can reverse established diabetes, highlighting its potential as a dual-action therapeutic agent. In addition, I examined Microporous Annealed Particle (MAP) scaffold development, demonstrating its biocompatibility and effectiveness in supporting islet cell viability and function both in vitro and in vivo, emphasizing their potential to enhance islet transplanta-tion success and immune regulation at the transplantation site. These findings contribute significantly to understanding and developing novel therapeutic strategies for T1D and of-fering insights into future research and clinical application directions.

PHD (Doctor of Philosophy)
Type 1 Diabetes (T1D), Therapeutic, Autoimmunity, Islet, Lacritin, Immunomodulatory Effect, T-cell-mediated Autoimmune Responses, Dual-action Therapeutic Agent, Islet Transplantation, MAP, dissociated islet cell.
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