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Cited by 8Extracellular vesicles in diseaseDown syndrome and intellectual disability researchAlzheimer's disease research and treatments

Extracellular Vesicle Treatment Alleviates Neurodevelopmental and Neurodegenerative Pathology in Cortical Spheroid Model of Down Syndrome

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Campbell, Natalie Baker, Patel, Yesha, Moore, Tara L., Medalla, Maria, Zeldich, Ella·2023·International Journal of Molecular Sciences
DOI 10.3390/ijms24043477PMC PMC9960302
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Abstract

Down syndrome (DS), or trisomy 21, is manifested in a variety of anatomical and cellular abnormalities resulting in intellectual deficits and early onset of Alzheimer’s disease (AD) with no effective treatments available to alleviate the pathologies associated with the disorder. The therapeutic potential of extracellular vesicles (EVs) has emerged recently in relation to various neurological conditions. We have previously demonstrated the therapeutic efficacy of mesenchymal stromal cell-derived EVs (MSC-EVs) in cellular and functional recovery in a rhesus monkey model of cortical injury. In the current study, we evaluated the therapeutic effect of MSC-EVs in a cortical spheroid (CS) model of DS generated from patient-derived induced pluripotent stem cells (iPSCs). Compared to euploid controls, trisomic CS display smaller size, deficient neurogenesis, and AD-related pathological features, such as enhanced cell death and depositions of amyloid beta (Aβ) and hyperphosphorylated tau (p-tau). EV-treated trisomic CS demonstrated preserved size, partial rescue in the production of neurons, significantly decreased levels of Aβ and p-tau, and a reduction in the extent of cell death as compared to the untreated trisomic CS. Together, these results show the efficacy of EVs in mitigating DS and AD-related cellular phenotypes and pathological depositions in human CS.

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  • Analyses of neural progenitor cells arising from trisomy 21 induced pluripotent stem cells have provided conflicting data, with some suggesting that apoptosis is increased and others seeing no effect.

    “Analyses of NPCs arising from T21 iPSCs have provided conflicting data, with some suggesting that apoptosis is increased74,79,95 and others seeing no effect75,77,81,96.”

    From Consequences of trisomy 21 for brain development in Down syndrome (2024) · cites this paper as [95]

    Results §2.2 reports no significant difference in NPC proliferation or numbers between trisomic and euploid cortical spheroids, but does not measure NPC apoptosis. Results §2.5 reports increased cell death across untreated trisomic spheroids; it does not establish whether apoptosis in NPCs specifically was affected. Thus our copy cannot verify the no-effect finding for NPC apoptosis attributed to this source. (LLM, conf=0.72)

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Authors
Campbell, N. B., Patel, Y., Moore, T. L., Medalla, M., & Zeldich, E.
Affiliations
  • Boston University (US)
  • University of Massachusetts Amherst (US)
Corresponding author
Zeldich, Ella
ORCID
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2023-02-09
Volume
24
Issue
4
Pages
3477
ISSN
1422-0067 (ISSN-L)
DOI
10.3390/ijms24043477
PMC
PMC9960302
OpenAlex
W4319983412
Cited by
8
References
98
Citations by year
2026: 2 · 2025: 2 · 2024: 2 · 2023: 2
FWCI
0.71
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Molecular Sciences (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
National Institutes of Health (R21-HD098542, R03-NS126864, R21-NS125469, R56-NS112207, R21-NS102991, R01-AG078460, R01-AG068168)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Down syndrome and intellectual disability research
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Keywords
Down syndrome, extracellular vesicles, Alzheimer's disease, amyloid-beta, hyperphosphorylated tau, neurogenesis, neurodegeneration, iPSC-derived neurons, cell death, cell therapy
MeSH terms
Extracellular Vesicles, Alzheimer Disease, Down Syndrome, Humans, Neurons, Amyloid beta-Peptides

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