ArticlePloS one2021
IFNγ-stimulated dendritic cell extracellular vesicles can be nasally administered to the brain and enter oligodendrocytes.
Article in PloS one, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 20 citations in OpenAlex.
- Formulation considerations in enhancing olfactory mucosal deposition for nose-to-brain drug delivery.Drug delivery and translational research · 2026Review
- Nose-to-brain drug delivery: from bench to bedside.Translational neurodegeneration · 2025Review
- Exosomes in epilepsy: bridging neuroinflammation, diagnosis, and therapeutic delivery.Frontiers in immunology · 2025Review
- Role of miRNAs in neurovascular injury and repair.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2024Review
- Review
- Lipid and Transcriptional Regulation in a Parkinson's Disease Mouse Model by Intranasal Vesicular and Hexosomal Plasmalogen-Based Nanomedicines.Advanced healthcare materials · 2024Article
- Rapid and Widespread Distribution of Intranasal Small Extracellular Vesicles Derived from Mesenchymal Stem Cells throughout the Brain Potentially via the Perivascular Pathway.Pharmaceutics · 2023Article
- Extracellular vesicles in the glioblastoma microenvironment: A diagnostic and therapeutic perspective.Molecular aspects of medicine · 2023Review
- Transnasal-brain delivery of nanomedicines for neurodegenerative diseases.Frontiers in drug delivery · 2023Review
- The human neurosecretome: extracellular vesicles and particles (EVPs) of the brain for intercellular communication, therapy, and liquid-biopsy applications.Frontiers in molecular biosciences · 2023Review
- Immunological Effects ofCells · 2022Article
- Exosomes as Natural Nanocarriers for RNA-Based Therapy and Prophylaxis.Nanomaterials (Basel, Switzerland) · 2022Review
- Therapeutic Applications of Extracellular Vesicles for Myocardial Repair.Frontiers in cardiovascular medicine · 2021Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Extracellular vesicles secreted from IFNγ-stimulated rat dendritic cells (referred to here as IFNγ-DC-EVs) contain miRNAs which promote myelination (including but not limited to miR-219), and preferentially enter oligodendrocytes in brain slice cultures. IFNγ-DC-EVs also increase myelination when nasally administered to naïve rats. While we can infer that these extracellular vesicles enter the CNS from functional studies, here we demonstrate biodistribution throughout the brain after nasal delivery by way of imaging studies. After nasal administration, Xenolight DiR-labelled IFNγ-DC-EVs were detected 30 minutes later throughout the brain and the cervical spinal cord. We next examined cellular uptake of IFNγ-DC-EVs by transfecting IFNγ-DC-EVs with mCherry mRNA prior to nasal administration. mCherry-positive cells were found along the rostrocaudal axis of the brain to the brainstem. These cells morphologically resembled oligodendrocytes, and indeed cell-specific co-staining for neurons, astrocytes, microglia and oligodendrocytes showed that mcherry positive cells were predominantly oligodendrocytes. This is in keeping with our prior in vitro results showing that IFNγ-DC-EVs are preferentially taken up by oligodendrocytes, and to a lesser extent, microglia. To confirm that IFNγ-DC-EVs delivered cargo to oligodendrocytes, we quantified protein levels of miR-219 mRNA targets expressed in oligodendrocyte lineage cells, and found significantly reduced expression. Finally, we compared intranasal versus intravenous delivery of Xenolight DiR-labelled IFNγ-DC-EVs. Though labelled IFNγ-DC-EVs entered the CNS via both routes, we found that nasal delivery more specifically targeted the CNS with less accumulation in the liver. Taken together, these data show that intranasal administration is an effective route for delivery of IFNγ-DC-EVs to the CNS, and provides additional support for their development as an EV-based neurotherapeutic that, for the first time, targets oligodendrocytes.
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Registered trials
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.