EFFECT OF PHOSPHOLIPIDS AND EXOSOMES ON NEURAL STEMCELLS DIFFERENTIATION UNDER OXIDATIVE STRESS

DELGADO S; BANCHIO, C

Salta

Congreso; SAIB; 2019

SAIB

Neural Stem Cells (NSC) have the capacity to generate and regenerate the nervous system. In the central nervous system, there are niches of NSC that are located mainly in the subventricular zone and in the hippocampus. In case of damage, these cells migrate to the site of the lesion and repair the damaged tissue. However, their capacity is limited, due to their partial potential to replace dead neurons and rebuild the dendritic connections. For these reasons, it is important to evaluate the mechanisms of differentiation for therapies development. Preliminary studies in our laboratory have demonstrated that certain bioactive lipids have a regulatory effect of the fate of NSC. On the other hand, exosomes have been described as a new model of cell communication, and become a novel treatment for several pathologies. In case of nervous system, several in vitro and in vivo studies have demonstrated the effects of exosomes derived from mesenchymal stem cells for the treatment of different nervous system injuries, such as stroke, traumatic brain injuries and neurodegenerative diseases such as Alzheimer and Parkinson. Using these two ideas, the aim is to evaluate the effect of certain lipids and exosomes on NSCs differentiation and proliferation under normal, oxidative stress or damage conditions. Mouse embryonic NSCs were exposed to different concentrations of hydrogen peroxide, ferrous sulfate and cupric sulfate to generate oxidative damage. Moreover, NSCs were cultivated in the presence of the phospholipids after the damage was induced to evaluate their neuroprotective effect. Finally, by immunofluorescence analysis using specific markers, we studied the effect of PtdCho during NSCs differentiation under stress microenvironment. In other hand, we demonstrated that treatment with exosomes isolated from neural stem cells promote neuronal differentiation without affecting glial differentiation. In addition, exosomes produce a significative increasing in primary neurite length. According to these results in non-stressed conditions both molecules can enhance neuronal differentiation but in reactive condition future studies are needed. Here we provide evidences that reinforce the role of lipids and exosomes as signaling molecules, opening new avenues to restoratives therapies.