Immunomodulation in Experimental Autoimmune Encephalomyelitis Using PEG-4MAL Hydrogel with Dendritic Cells: Effects of Variable Stimuli on Cell Maturation

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DAMICO-THESIS-2024.pdf (1.74 MB)
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Damico, Abigail G.
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Wallace H. Coulter Department of Biomedical Engineering
The joint Georgia Tech and Emory department was established in 1997
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https://hdl.handle.net/1853/78603
Abstract
Over the recent decades, research in biomaterials and immunoengineering has been investigated at a higher rate than previous years in science. Due to this there has been a surge of development in advanced therapies to treat cancers, autoimmune diseases, and other possible immune-related pathologies. Dendritic cells (DCs) have been at the forefront of pharmaceutical and biological therapeutics, as a bridge between the innate and adaptive immune system. In cell therapy, DCs have a high efficacy especially when being used for cell transplantation, vaccines, tumor clearance, and autoimmunity. Dr. Julia Babensee has pioneered research in biomaterial adjuvant effect with DCs, which was a novel discovery and elicited subsequent research interests by other investigators in the use of biomaterial stimulation of autoimmunity, focusing on biomaterials that promote tolerance. This research thesis therefore sought to contribute towards the ongoing research in the Babensee lab, which focuses on developing a biomaterial system to ameliorate autoimmunity, with the biomaterial system being applied to the condition of Multiple Sclerosis. The biomaterial system is combined of poly (ethylene glycol)- 4 arms maleimide (PEG-4MAL) hydrogels conjugated with the immunosuppressive cytokine, interleukin, IL-10, which is injectable, in situ cross linkable and degradable system for localized delivery of immunosuppressive DCs. Therefore, it is important to understand how IL-10, and other treatments may affect the migration of DCs, through the hydrogel, and through the body. With mature DCs (mDCs) known to have better migration abilities, the use of a maturation stimulus may be needed as an addition of tolerogenic DCs. Poly (ethylene glycol) is being used in this study due to its unique attributes, such as a branched macromer precursor, with each arm being conjugated to a maleimide group (PEG-4MAL) which allows for the bioconjugation of crosslinkers, adhesive ligands, growth factors and cytokines. The hydrogels allow for the DCs to be protected from inflammation that may occur and enhance the cell viability in vivo. The amount of IL-10 incorporated in the hydrogel has been shown to maintain incorporated DC viability. Based on preliminary results previously conducted in the laboratory, hydrogels loaded with IL-10 and encapsulated DC10s were shown to have an effect of the clinical score and body weight of mice compared to mice without any treatment [2]. The benefit of the biomaterial system was apparent from the decrease in clinical scores, as well as histological studies. In the current studies, we address the potential of the biomaterial system to ameliorate EAE symptoms, and potential stimulation of pretreated DCs obstacles. Henceforth, these studies focused on characterizing the late-stage immune cell response post injection in an autoimmune situation, and procedures to follow for comparable results to previous studies, as well as optimal maturation and immunosuppressive stimulus for migration of DCs.
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2024-07-27
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