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INVESTIGATION OF HUMAN NEURAL STEM CELL-DERIVED EXTRACELLULAR VESICLES TO AMELIORATE COMBINED CRANIAL RADIATION- AND CHEMO-THERAPY-INDUCED COGNITIVE IMPAIRMENTS
Date of Award
Restricted Thesis: Campus only access
Master of Science in Biology
First Reader/Committee Chair
Cancer is a serious disease that affects many people. Recent advancements in successful cancer treatment strategies significantly improved the survival of patients. However, these approaches do not come without risks. One of the serious side effects includes combined cranial radiation- and chemo-therapy-induced cognitive dysfunction. A hallmark of this cognitive dysfunction is neuroinflammation and a decrease in synaptic density and dendritic complexity. Previously, we have shown that intracranial injection of human neural stem cells (hNSC) imparts neurotrophic benefits to the damaged brain. We hypothesize that neuroprotective benefits, in part, are derived from extracellular vesicles secreted by the hNSCs. In this study, we used the systemic injection of three different GMP-grade hNSC-derived extracellular vesicles (hNSC-EVs) to reduce neuroinflammation and protect from reductions in synaptic density and cognitive dysfunction in immunocompetent wild-type mice treated with combined radiation and chemotherapy. To assess the level of cognitive decrements caused by this treatment, and the benefit from the EVs, mice were administered five different behavior tests and three different immunofluorescent staining. We found that radiation and chemotherapy had a detrimental effect on cognitive function, and the EV treatment improved cognitive function in mice. The IHC results showed a positive correlation between the radiation and chemotherapy treatments and increased levels of neuroinflammation and decreased synaptic density. In contrast, the EV-treated mice showed reduced neuroinflammation and increased synaptic density. This data supports using hNSC derived-EVs to protect against behavioral and molecular effects from radiation and chemotherapy.
Hudson, Casey, "INVESTIGATION OF HUMAN NEURAL STEM CELL-DERIVED EXTRACELLULAR VESICLES TO AMELIORATE COMBINED CRANIAL RADIATION- AND CHEMO-THERAPY-INDUCED COGNITIVE IMPAIRMENTS" (2023). Electronic Theses, Projects, and Dissertations. 1787.