NSC EXOSOMES REGULATE NEURONAL DIFFERENCIATION

DELGADO S; BANCHIO, C

Congreso; SAIB; 2020

Exosomes are small extracellular vesicles (30-100 nm) derived from the endosome system. The exosome membrane is a lipid bilayer that contains cholesterol, sphingomyelin, and ceramide in association with proteins, and in the lumen they contain proteins, DNA, and RNA (noncoding mRNA, miRNA, and RNA). Exosomes have been shown to mediate communication between neurons, glial cells, and between neurons and glial cells. The latter plays an essential role in maintaining neuronal activity; for example, exosomes secreted by oligodendrocytes, after being endocytic by neurons, regulate metabolism and viability in situations of oxidative stress or nutrient deprivation. Astrocytes, for their part, regulate brain development and function by regulating synapses formation and neurites growth. At present, various in vitro and in vivo studies have demonstrated the therapeutic effects of treatment with exosomes derived from mesenchymal stem cells in different conditions of the nervous system, such as cerebrovascular accident, head trauma encephalic and neurodegenerative diseases such as Alzheimer´s and Parkinson´s. However, despite these results, the effect of exosomes may vary depending on the tissue from which the stem cells are isolated as well as the microenvironment to which they are exposed. As a general objective we propose to decipher the effect of exosomes extracted from stem cells on neuronal stem cell (NSCs) proliferation and differentiation. We purified exosomes from NSCs culture, and analyzed the quality by western blot, transmission electron microcopy (TEM) and dynamic light scattering (DLS). To evaluate the effect on NSCs differentiation, cells were plated under differentiation conditions and supplemented with exosomes. After 24 hs we performed immunocytochemistry to evaluate neuronal differentiation. We demonstrated that NSCs exosomes but not fibroblast exosomes induce neuronal differentiation. In addition, exosomes treatment increases the neurite length. In conclusion, NSCs-exosomes could regulate stem cell differentiation.