Exosomes derived from astrocytes after oxygen-glucose deprivation promote differentiation and migration of oligodendrocyte precursor cells in vitro

Abstract

Background: Excessive release of glutamate, oxidative stress, inflammation after ischemic brain injury can lead to demyelination. Astrocytes participate in the maturation and differentiation of oligodendrocyte precursor cells (OPCs), and play multiple roles in the process of demyelination and remyelination. Here, we studied the role of Astrocyte-derived exosomes (AS-Exo) under ischemic conditions in proliferation, differentiation and migration of OPCs in vitro.

Methods and results: Exosomes were collected from astrocytes supernatant by differential centrifugation from control astrocytes (CT^exo), mild hypoxia astrocytes (O2R24^exo) which were applied oxygen-glucose deprivation for 2 h and reperfusion for 24 h (OGD2hR24h) and severe hypoxia astrocytes (O4R24^exo) which were applied oxygen-glucose deprivation for 4 h and reperfusion for 24 h (OGD4hR24h). Exosomes (20 µg/ml) were co-cultured with OPCs for 24 h and their proliferation, differentiation and migration were detected. The results showed that AS-Exo under severe hypoxia (O4R24^exo) inhibit the proliferation of OPCs. Meanwhile, all exosomes from three groups can promote OPCs differentiation and migration. Compared to control, the expressions of MAG and MBP, markers of mature oligodendrocytes, were significantly increased in AS-Exo treatment groups. AS-Exo treatment significantly increased chemotaxis for OPCs.

Conclusions: AS-Exo improve OPCs' differentiation and migration, whereas AS-Exo with severe hypoxic precondition suppress OPCs' proliferation. AS-Exo may be a potential therapeutic target for myelin regeneration and repair in white matter injury or other demyelination related diseases.

Keywords: Astrocyte-derived exosomes; Differentiation; Migration; Oligodendrocyte precursor cells; Oxygen-glucose deprivation; Proliferation.