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Cells
Volume 14
Issue 17
10.3390/cells14171304
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Human Adipose-Stem-Cell-Derived Small Extracellular Vesicles Modulate Behavior and Glial Cells in Young and Aged Mice Following TBI

by
Salma S. Abdelmaboud
1,2,
Lauren D. Moss
2,
Charles Hudson
3,
Rekha Patel
3,
Marta Avlas
2,
Jessica Wohlfahrt
4,
Tiara Wolf
4,
Jennifer Guergues
4,
Stanley M. Stevens, Jr.
4,
Niketa A. Patel
3,5 and
Paula C. Bickford
1,2,3,*
1
Department of Molecular Pharmacology and Physiology, University of South Florida Morsani College of Medicine, Tampa, FL 33612, USA
2
Department of Neurosurgery, Brain and Spine, University of South Florida Morsani College of Medicine, Tampa, FL 33612, USA
3
James A. Haley Veterans Hospital, Research Service, Tampa, FL 33637, USA
4
Department of Molecular Biosciences, University of South Florida, Tampa, FL 33620, USA
5
Department of Molecular Medicine, University of South Florida Morsani College of Medicine, Tampa, FL 33612, USA
*
Author to whom correspondence should be addressed.
Cells 2025, 14(17), 1304; https://doi.org/10.3390/cells14171304
Submission received: 27 May 2025 / Revised: 5 August 2025 / Accepted: 15 August 2025 / Published: 22 August 2025
(This article belongs to the Special Issue Glial Cells: Physiological and Pathological Perspective)
Versions Notes

Abstract

Traumatic brain injury (TBI) is a major cause of long-term neurological impairment, with aging amplifying vulnerability and worsening recovery. Older individuals face greater cognitive and motor deficits post-TBI and respond less effectively to treatments, as both aging and TBI independently elevate neuroinflammation and cognitive decline. This study evaluated the therapeutic effects of human adipose-derived stem cell small extracellular vesicles (hASC-sEVs) on neurological recovery and neuroinflammation in a mouse model of TBI. Male C57BL/6 mice (3, 15, and 20 months old) underwent controlled cortical impact (CCI) and received intranasal hASC-sEVs 48 h post-injury; control groups received PBS. A dose–response study at 7 days post injury (dpi) identified 20 µg as the optimal therapeutic dose, improving motor function, reducing neuroinflammation, and enhancing neurogenesis. This was followed by a 30-dpi study assessing cognitive function, neuroinflammation, neurogenesis, and proteomic changes in microglia and astrocytes via mass spectrometry. hASC-sEV treatment significantly improved behavioral outcomes and reduced neuroinflammatory markers (GFAP, IBA-1, and MHC-II), with reduced efficacy observed 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.
Keywords: TBI; aged; small extracellular vesicles (sEVs); human adipose derived stem cells (hASC); microglia; astrocytes; neuroinflammation TBI; aged; small extracellular vesicles (sEVs); human adipose derived stem cells (hASC); microglia; astrocytes; neuroinflammation

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MDPI and ACS Style

Abdelmaboud, S.S.; Moss, L.D.; Hudson, C.; Patel, R.; Avlas, M.; Wohlfahrt, J.; Wolf, T.; Guergues, J.; Stevens, S.M., Jr.; Patel, N.A.; et al. Human Adipose-Stem-Cell-Derived Small Extracellular Vesicles Modulate Behavior and Glial Cells in Young and Aged Mice Following TBI. Cells 2025, 14, 1304. https://doi.org/10.3390/cells14171304

AMA Style

Abdelmaboud SS, Moss LD, Hudson C, Patel R, Avlas M, Wohlfahrt J, Wolf T, Guergues J, Stevens SM Jr., Patel NA, et al. Human Adipose-Stem-Cell-Derived Small Extracellular Vesicles Modulate Behavior and Glial Cells in Young and Aged Mice Following TBI. Cells. 2025; 14(17):1304. https://doi.org/10.3390/cells14171304

Chicago/Turabian Style

Abdelmaboud, Salma S., Lauren D. Moss, Charles Hudson, Rekha Patel, Marta Avlas, Jessica Wohlfahrt, Tiara Wolf, Jennifer Guergues, Stanley M. Stevens, Jr., Niketa A. Patel, and et al. 2025. "Human Adipose-Stem-Cell-Derived Small Extracellular Vesicles Modulate Behavior and Glial Cells in Young and Aged Mice Following TBI" Cells 14, no. 17: 1304. https://doi.org/10.3390/cells14171304

APA Style

Abdelmaboud, S. S., Moss, L. D., Hudson, C., Patel, R., Avlas, M., Wohlfahrt, J., Wolf, T., Guergues, J., Stevens, S. M., Jr., Patel, N. A., & Bickford, P. C. (2025). Human Adipose-Stem-Cell-Derived Small Extracellular Vesicles Modulate Behavior and Glial Cells in Young and Aged Mice Following TBI. Cells, 14(17), 1304. https://doi.org/10.3390/cells14171304

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