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Enhanced Stem Cell Repair of Nervous Tissue: Feasibility of a PLGA Microsphere SDF-1 Dosing Transdermal Microneedle Patch

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2020-09-29

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Mayranen, Christopher. 2020. Enhanced Stem Cell Repair of Nervous Tissue: Feasibility of a PLGA Microsphere SDF-1 Dosing Transdermal Microneedle Patch. Master's thesis, Harvard Extension School.

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Abstract

Here is evaluated a strategy for stem cell repair of nervous tissue with a potential therapeutic application of a transdermal microneedle stromal-derived-factor 1 (SDF-1) chemokine delivery system. The central question of this research focuses on whether enhanced SDF-1 signaling to mesenchymal stem cells (MSCs) at injury sites promotes more effective regeneration of damaged nerves. SDF-1/CXCL12 is a potent chemokine protein known to bind to ligands CXCR4 and CXCR7, both of which are proven to drive processes involved with nervous tissue regeneration (Carbajal 2010). While it is shown that SDF-1 delivery systems can facilitate repair of nerves, many of the mechanisms behind this are still unclear (Purcell 2012). In all studies evaluated in this work, significant neuro-regenerative improvements were seen as: improved MSC chemotaxis, greater volumes of repairing cells at injury sites, and an improved quality of injury repair. Many factors and cell types are also involved in nerve repair and each injury involves a coordination of signaling and checkpoints (Jiang 2017, Sullivan 2016). This study looks closely at specific nervous tissue damage and repair systems, finding that, in all cases, SDF-1 supplementation improves neural regeneration. This study concludes that further investigation of timed-release SDF-1 in microspheres via microneedle patch, using the tested approaches described here, is warranted to understand diffusion rates, cell signaling, inflammation response, fibrosis, and bio-compatibility of such a repair system.

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Acute axonal degeneration (AAD), Astrocyte, Chemokine, Demyelination, Enhanced regeneration, Functionalization, Hydrogel, Macrophage, Mesenchymal stem cell (MSC), Microvesicles, Neurotrophic factor, Oligodendrocyte, Polylactide-co-glycolide (PLGA), Reactive gliosis, Schwann cell, Sciatic nerve, Secondary injury, Stromal-derived-factor (SDF1), Wallerian degeneration

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