ArticleFrontiers in molecular neuroscience2022
Proficiency of Extracellular Vesicles From hiPSC-Derived Neural Stem Cells in Modulating Proinflammatory Human Microglia: Role of Pentraxin-3 and miRNA-21-5p.
Article in Frontiers in molecular neuroscience, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 25 citations in OpenAlex.
- Article
- Intranasal Human NSC-Derived EVs Therapy Can Restrain Inflammatory Microglial Transcriptome, and NLRP3 and cGAS-STING Signalling, in Aged Hippocampus.Journal of extracellular vesicles · 2026Article
- Molecular and functional characterization of GMP-manufactured neural stem cells and their extracellular vesicles for innovative therapeutic applications.Stem cell research & therapy · 2026Article
- Role of extracellular vesicle-carried ncRNAs in the interactive 'dialogue' within the brain and beyond: emerging theranostic epigenetic modifiers in brain-derived nanoplatforms.Translational neurodegeneration · 2025Review
- Most L1CAM Is not Associated with Extracellular Vesicles in Human Biofluids and iPSC-Derived Neurons.Molecular neurobiology · 2025Article
- Extracellular vesicles from hiPSC-derived NSCs protect human neurons against Aβ-42 oligomers induced neurodegeneration, mitochondrial dysfunction and tau phosphorylation.Stem cell research & therapy · 2025Article
- Neural stem cell-derived small extracellular vesicles: a new therapy approach in neurological diseases.Frontiers in immunology · 2025Review
- Extracellular vesicles from human-induced pluripotent stem cell-derived neural stem cells alleviate proinflammatory cascades within disease-associated microglia in Alzheimer's disease.Journal of extracellular vesicles · 2024Article
- Promise of mesenchymal stem cell-derived extracellular vesicles for alleviating subarachnoid hemorrhage-induced brain dysfunction by neuroprotective and antiinflammatory effects.Brain, behavior, & immunity - health · 2024Review
- Extracellular vesicles as therapeutics for inflammation and infection.Current opinion in biotechnology · 2024Review
- Extracellular vesicles from hiPSC-NSCs can prevent peripheral inflammation-induced cognitive dysfunction with inflammasome inhibition and improved neurogenesis in the hippocampus.Journal of neuroinflammation · 2023Article
- Small Extracellular Vesicles Derived from Induced Pluripotent Stem Cells in the Treatment of Myocardial Injury.International journal of molecular sciences · 2023Review
- Biodelivery of therapeutic extracellular vesicles: should mononuclear phagocytes always be feared?Frontiers in cell and developmental biology · 2023Review
- Intranasally administered extracellular vesicles from human induced pluripotent stem cell-derived neural stem cells quickly incorporate into neurons and microglia in 5xFAD mice.Frontiers in aging neuroscience · 2023Article
- Enhancing Cutaneous Wound Healing Based on Human Induced Neural Stem Cell-derived Exosomes.International journal of nanomedicine · 2022Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Extracellular vesicles (EVs) shed by human-induced pluripotent stem cell (hiPSC)-derived neural stem cells (hNSC-EVs) have shown potent antiinflammatory properties in a mouse macrophage assay and a mouse model of acute neuroinflammation. They can also quickly permeate the entire brain after intranasal administration, making them attractive as an autologous or allogeneic off-the-shelf product for treating neurodegenerative diseases. However, their ability to modulate activated human microglia and specific proteins and miRNAs mediating antiinflammatory effects of hNSC-EVs are unknown. We investigated the proficiency of hNSC-EVs to modulate activated human microglia and probed the role of the protein pentraxin 3 (PTX3) and the miRNA miR-21-5p within hNSC-EVs in mediating the antiinflammatory effects. Mature microglia generated from hiPSCs (iMicroglia) expressed multiple microglia-specific markers. They responded to lipopolysaccharide (LPS) or interferon-gamma challenge by upregulating tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) mRNA expression and protein release. iMicroglia also exhibited proficiency to phagocytose amyloid-beta (Aβ). The addition of hNSC-EVs decreased TNF-α and IL-1β mRNA expression and the release of TNF-α and IL-1β by LPS-stimulated iMicroglia (proinflammatory human Microglia). However, the antiinflammatory activity of hNSC-EVs on LPS-stimulated microglia was considerably diminished when the PTX3 or miR-21-5p concentration was reduced in EVs. The results demonstrate that hNSC-EVs are proficient for modulating the proinflammatory human microglia into non-inflammatory phenotypes, implying their utility to treat neuroinflammation in neurodegenerative diseases. Furthermore, the role of PTX3 and miR-21-5p in the antiinflammatory activity of hNSC-EVs provides a new avenue for improving the antiinflammatory effects of hNSC-EVs through PTX3 and/or miR-21-5p overexpression.
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