Glial phenotype induction of neural stem progenitor cells using astrocyte-derived exosomes

Exosomes, small vescicles with a lipid bilayer, are released from many cell types and are part of the cell secretrome that can play a role in intercellular communication. They originate from cytoplasmic multivescicular bodies, fuse with the plasma membrane and release their content of lipids, proteins and RNAs in the extracellular space or in target cells. A growing body of evidence suggests that exosomes contribute to many aspects of healthy and pathological cells, and they may influence the homeostasis of target cells. With the aim of understanding the role of exosomes during tissue development, we investigated the role of these extracellular vesicles in neural progenitor stem cells (NSPCs) commitment. By using NSPCs from embryonic mouse spinal cord, we demostrate that neuronal and/or astrocytes induction of differentiation may be modulated by exosomes obtained from astrocytes. Treatment of proliferating NSPCs with exosomes, produced and released by differentiated cells, triggers cell differentiation toward astrocytic phenotype, as demostrated by glial and neuronal marker expression. The same effect can also be observed upon growth factor withdrawal, a condition in which NSPCs may autonomously differentiate in a mixed population of neurons and glial cells. We also show that the effect of exosomes treatment is dose-dependent.