Extracellular vesicles containing the transferrin receptor as nanocarriers of apotransferrin.
Adult
Animals
Apoproteins
/ administration & dosage
Astrocytes
/ drug effects
Cell Line, Transformed
Cell Line, Tumor
Cells, Cultured
Extracellular Vesicles
/ metabolism
Female
Humans
Male
Mice
Nanoparticles
/ administration & dosage
Rats
Rats, Wistar
Receptors, Transferrin
/ administration & dosage
Transferrin
/ administration & dosage
dynamic light scattering
exosomes
extracellular vesicles
scanning electron microscopy
size-exclusion chromatography
transferrin
transferrin receptor 1
Journal
Journal of neurochemistry
ISSN: 1471-4159
Titre abrégé: J Neurochem
Pays: England
ID NLM: 2985190R
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
25
10
2019
revised:
28
02
2020
accepted:
25
03
2020
pubmed:
6
4
2020
medline:
11
3
2021
entrez:
6
4
2020
Statut:
ppublish
Résumé
Previous work by our group has shown the pro-differentiating effects of apotransferrin (aTf) on oligodendroglial cells in vivo and in vitro. Further studies showed the remyelinating effect of aTf in animal demyelination models such as hypoxia/ischemia, where the intranasal administration of human aTf provided brain neuroprotection and reduced white matter damage, neuronal loss, and astrogliosis in different brain regions. These data led us to search for a less invasive and controlled technique to deliver aTf to the CNS. To such end, we isolated extracellular vesicles (EVs) from human and mouse plasma and different neuron and glia conditioned media and characterized them based on their quality, quantity, identity, and structural integrity by western blot, dynamic light scattering, and scanning electron microscopy. All sources yielded highly pure vesicles whose size and structures were in keeping with previous literary evidence. Given that, remarkably, EVs from all sources analyzed contained Tf receptor 1 (TfR1) in their composition, we employed two passive cargo-loading strategies which rendered successful EV loading with aTf, specifically through binding to TfR1. These results unveil EVs as potential nanovehicles of aTf to be delivered into the CNS parenchyma, and pave the way for further studies into their possible clinical application in the treatment of demyelinating diseases.
Substances chimiques
Apoproteins
0
Receptors, Transferrin
0
Transferrin
0
apotransferrin
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
327-338Informations de copyright
© 2020 International Society for Neurochemistry.
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