Extracellular vesicles containing the transferrin receptor as nanocarriers of apotransferrin

VANESA S. MATTERA1 | PEHUÉN PEREYRA GERBER2 | ROMINA GLISONI3,4 | MATIAS OSTROWSKI2 | SANDRA V. VERSTRAETEN1,5 | JUANA M. PASQUINI1,5* | JORGE D. CORREALE6*

JOURNAL OF NEUROCHEMISTRY

WILEY-BLACKWELL PUBLISHING, INC

Lugar: Londres; Año: 2020 vol. 155 p. 327 - 338

0022-3042

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 theremyelinating effect of aTf in animal demyelination models such as hypoxia/ischemia,where the intranasal administration of human aTf provided brain neuroprotectionand reduced white matter damage, neuronal loss, and astrogliosis in different brainregions. These data led us to search for a less invasive and controlled technique todeliver aTf to the CNS. To such end, we isolated extracellular vesicles (EVs) fromhuman and mouse plasma and different neuron and glia conditioned media and characterizedthem based on their quality, quantity, identity, and structural integrity bywestern blot, dynamic light scattering, and scanning electron microscopy. All sourcesyielded highly pure vesicles whose size and structures were in keeping with previousliterary evidence. Given that, remarkably, EVs from all sources analyzed contained Tfreceptor 1 (TfR1) in their composition, we employed two passive cargo-loading strategieswhich rendered successful EV loading with aTf, specifically through binding toTfR1. These results unveil EVs as potential nanovehicles of aTf to be delivered intothe CNS parenchyma, and pave the way for further studies into their possible clinicalapplication in the treatment of demyelinating diseases