Graduation Year
2025
Document Type
Dissertation
Degree
Ph.D.
Degree Name
Doctor of Philosophy (Ph.D.)
Degree Granting Department
Medical Sciences
Major Professor
Paula C. Bickford, Ph.D.
Committee Member
Stanley M. Stevens Jr, Ph.D.
Committee Member
Travis Jackson, Ph.D.
Committee Member
Yao Yao, Ph.D.
Keywords
TBI, Aged, Small extracellular vesicles (sEVs), human Adipose derived stem cells (hASC), Microglia, Astrocytes, Neuroinflammation
Abstract
Traumatic brain injury (TBI) is a leading cause of long-term neurological impairment, with aging significantly increasing vulnerability and worsening outcomes. Older individuals experience greater cognitive and motor deficits after TBI and often show diminished responses to therapeutic interventions. Both aging and TBI independently promote heightened neuroinflammation and cognitive dysfunction, increasing susceptibility to poor recovery. This study investigated the therapeutic potential of small extracellular vesicles (sEVs) derived from human adipose-derived stem cells (hASCs) to promote neurological recovery and modulate neuroinflammation in a mouse model of TBI. Male C57BL/6 mice aged 3, 15, and 20 months underwent controlled cortical impact (CCI) and received intranasal (IN) hASC-sEVs at 48 hours post-injury; control groups (sham and TBI) received PBS. An initial dose-response study at 7 days post-injury (dpi) identified 20 µg as the optimal therapeutic dose based on improvements in motor function, neuroinflammatory markers, and neurogenesis. This was followed by an extended study to 30 dpi to assess cognitive performance, neuroinflammation, neurogenesis, and proteomic changes in isolated microglia and astrocytes using mass spectrometry. hASC-sEV treatment significantly improved cognitive and motor outcomes and reduced neuroinflammatory markers (GFAP, IBA-1) in the cortex, hippocampus, and (MHC-II) in thalamus, although these effects were less pronounced in older mice. Proteomics revealed that hASC-sEVs reduce inflammatory proteins (TNF-α, IL-1β, IFNG, CCL2), and modulated mitochondrial dysfunction and reactive oxygen species. These results highlight hASC-sEVs as a promising cell-free therapy for improving TBI outcomes, especially in aging populations
Scholar Commons Citation
Abdelmaboud, Salma S., "Human Adipose Stem Cell-Derived Small Extracellular Vesicles Modulate Glial Cell Response in Aged and Young TBI Mouse Models" (2025). USF Tampa Graduate Theses and Dissertations.
https://digitalcommons.usf.edu/etd/11028
