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Cited by 50Extracellular vesicles in diseaseTraumatic Brain Injury and Neurovascular DisturbancesTraumatic Brain Injury Research

Extracellular Vesicles Derived From Neural Stem Cells, Astrocytes, and Microglia as Therapeutics for Easing TBI-Induced Brain Dysfunction

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Hering, Catherine, Shetty, Ashok K·2023·Stem Cells Translational Medicine
DOI 10.1093/stcltm/szad004PMC PMC10021503
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Abstract

Extracellular vesicles (EVs) derived from neural stem cells (NSC-EVs), astrocytes (ADEVs), and microglia (MDEVs) have neuroregenerative properties. This review discusses the therapeutic efficacy of NSC-EVs, ADEVs, and MDEVs in traumatic brain injury (TBI) models. The translational value and future directions for such EV therapy are also deliberated. Studies have demonstrated that NSC-EV or ADEV therapy can mediate neuroprotective effects and improve motor and cognitive function after TBI. Furthermore, NSC-EVs or ADEVs generated after priming parental cells with growth factors or brain-injury extracts can mediate improved therapeutic benefits. However, the therapeutic effects of naïve MDEVs are yet to be tested rigorously in TBI models. Studies using activated MDEVs have reported both adverse and beneficial effects. NSC-EV, ADEV, or MDEV therapy for TBI is not ready for clinical translation. Rigorous testing of their efficacy for preventing chronic neuroinflammatory cascades and enduring motor and cognitive impairments after treatment in the acute phase of TBI, an exhaustive evaluation of their miRNA or protein cargo, and the effects of delayed EV administration post-TBI for reversing chronic neuroinflammation and enduring brain impairments, are needed. Moreover, the most beneficial route of administration for targeting EVs into different neural cells in the brain after TBI and the efficacy of well-characterized EVs from NSCs, astrocytes, or microglia derived from human pluripotent stem cells need to be evaluated. EV isolation methods for generating clinical-grade EVs must also be developed. Overall, NSC-EVs and ADEVs promise to mitigate TBI-induced brain dysfunction, but additional preclinical studies are needed before their clinical translation.

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Cited by

Sorted by citations

Authors
Hering, C., & Shetty, A. K.
Affiliations
Texas A&M Health Science Center (US)
Corresponding author
Shetty, Ashok K
ORCID
Venue
Stem Cells Translational Medicine
Publisher
Oxford University Press (OUP)
Published
2023-02-27
Volume
12
Issue
3
Pages
140-153
ISSN
  • 2157-6564 (ISSN-L)
  • 2157-6580
DOI
10.1093/stcltm/szad004
PMC
PMC10021503
OpenAlex
W4322496481
Cited by
50
References
5
Citations by year
2026: 11 · 2025: 16 · 2024: 17 · 2023: 6
FWCI
1.32
Type
journal article
Language
en
Open access
Licence
Locations
  • Stem Cells Translational Medicine (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
National Institutes of Health (NINDS-R01NS106907, NIA-RF1AG074256, NIA-R01AG075440)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
  • Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
  • Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
Keywords
extracellular vesicles, traumatic brain injury, neural stem cells, astrocytes, microglia, nerve regeneration, neuroprotection, neuroinflammation, motor and cognitive impairment, cell priming, EV isolation, clinical translation, human pluripotent stem cells
MeSH terms
Extracellular Vesicles, Animals, Astrocytes, Brain, Disease Models, Animal, Humans, Microglia, Neural Stem Cells

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