Extracellular vesicles as nanocarriers of apoTransferrin in demyelinating diseases

VANESA MATTERA; JUANA PASQUINI; JORGE CORREALE

Virtual

Congreso; ASN 2021 meeting; 2021

Extracellular vesicles (EVs) are lipid bilayer-delimited particles which are fundamental for intercellular communication. EVs capacity for biologic information transfer makes them an attractive tool as therapeutic agents for nanodelivery of different molecules to target cells. They are able to cross the blood brain barrier, their structure is biocompatible, and the cargo is protected from degradation, which increases molecule stability, solubility and bio-availability.Previous work by our group has shown the pro-differentiating effects of apoTransferrin (aTf) on oligodendroglial cells in vivo and in vitro. The remyelinating effect of aTf was also observed in a model of hypoxia/ischemia where aTf was intranasally administered. In this scenario, the purpose of this work is to establish the effect of nano-particles loaded with human aTf in a model of demyelination induced by cuprizone (CPZ).EVs were isolated from mouse plasma and characterized by Western blot, dynamic light scattering and scanning electron microscopy. Isolated EVs containing the Tf receptor 1 (TfR1) were loaded with aTf, specifically through binding to TfR1, using two passive cargo-loading strategies which rendered EV-Tf loaded particles. In this work, we show the promaturation effect of the EV-Tf system on oligodendroglial primary cultures and its remyelinating effect through intranasal administration in CPZ-demyelinated mice, as assessed through different cell markers and myelin staining.These results show 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.