Evidence map›Paper›PMID 33676561›Full record

ArticleAlzheimer's research & therapy2021

Human neural stem cell-derived extracellular vesicles mitigate hallmarks of Alzheimer's disease.

Lauren A Apodaca, Al Anoud D Baddour, Camilo Garcia, Leila Alikhani, Erich Giedzinski, Ning Ru, Anshu Agrawal, Munjal M Acharya, Janet E Baulch

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Alzheimer's research & therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.

0numbers the graph read from it
0cells of the map it votes in
71citing papers in PubMed
5.5field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

71 citing papers in PubMed, 97 citations in OpenAlex.

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  13. Extracellular vesicle-based therapies for neurodegenerative diseases.NeuroImmune pharmacology and therapeutics · 2025
    Review
  14. Review
  15. Stem cell and gene therapies for leukodystrophies.Molecular therapy. Methods & clinical development · 2025
    Review
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  17. Article
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  20. Review

11 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 1 institution in 1 country.

Lauren A ApodacaDepartment of Radiation Oncology, University of California Irvine, Irvine, CA, 92697, USA.
Al Anoud D BaddourDepartment of Radiation Oncology, University of California Irvine, Irvine, CA, 92697, USA.
Camilo GarciaDepartment of Radiation Oncology, University of California Irvine, Irvine, CA, 92697, USA.
Leila AlikhaniDepartment of Radiation Oncology, University of California Irvine, Irvine, CA, 92697, USA.
Erich GiedzinskiDepartment of Radiation Oncology, University of California Irvine, Irvine, CA, 92697, USA.
Ning RuDepartment of Radiation Oncology, University of California Irvine, Irvine, CA, 92697, USA.
Anshu AgrawalDepartment of Medicine, University of California Irvine, Irvine, CA, 92697, USA.
Munjal M AcharyaDepartment of Radiation Oncology, University of California Irvine, Irvine, CA, 92697, USA. macharya@uci.edu.
Janet E BaulchDepartment of Radiation Oncology, University of California Irvine, Irvine, CA, 92697, USA. jbaulch@uci.edu.ORCID 0000-0002-1078-6946
University of California, Irvine · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundRegenerative therapies to mitigate Alzheimer's disease (AD) neuropathology have shown very limited success. In the recent era, extracellular vesicles (EVs) derived from multipotent and pluripotent stem cells have shown considerable promise for the treatment of dementia and many neurodegenerative conditions.

methodsUsing the 5xFAD accelerated transgenic mouse model of AD, we now show the regenerative potential of human neural stem cell (hNSC)-derived EVs on the neurocognitive and neuropathologic hallmarks in the AD brain. Two- or 6-month-old 5xFAD mice received single or two intra-venous (retro-orbital vein, RO) injections of hNSC-derived EVs, respectively.

resultsRO treatment using hNSC-derived EVs restored fear extinction memory consolidation and reduced anxiety-related behaviors 4-6 weeks post-injection. EV treatment also significantly reduced dense core amyloid-beta plaque accumulation and microglial activation in both age groups. These results correlated with partial restoration of homeostatic levels of circulating pro-inflammatory cytokines in the AD mice. Importantly, EV treatment protected against synaptic loss in the AD brain that paralleled improved cognition. MiRNA analysis of the EV cargo revealed promising candidates targeting neuroinflammation and synaptic function.

conclusionsCollectively, these data demonstrate the neuroprotective effects of systemic administration of stem cell-derived EVs for remediation of behavioral and molecular AD neuropathologies.

Indexed as

Alzheimer DiseaseExtracellular VesiclesNeural Stem CellsAnimalsDisease Models, AnimalExtinction, PsychologicalFearHumansMiceMice, TransgenicAlzheimer’s diseaseExtracellular vesicleInflammatory responseNeural stem cell

Identifiers

PMID33676561
PMCPMC7937214
OpenAlexW3135053615

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.