GHRELIN ENHANCES GLIAL CONDITIONED MEDIA EFFECTS ON NEURAL MARKER EXPRESSION OF ADIPOSE-DERIVED MESENCHYMAL STEM CELLS.

Ghrelin (Ghre) is an orexigenic peptide playing an important role within the olfactory system and in some neuronal populations of the hypothalamus, amygdala and hippocampus. Recently, it attracted particular interest for its neuroprotective, antioxidant, anti-inflammatory and anti-apoptotic properties. Our previous study showed that conditioned medium (CM) from glial cells, such as Schwann cells (SCs) and Olfactory Ensheathing Cells (OECs) promotes a neural differentiation of Adipose-derived mesenchymal Stem Cells (ASCs). Here, we evaluated the effect of Ghre on ASCs isolated from human lipoaspirate. Results obtained in ASCs cultured either in the basal medium or in OEC-CM or SC-CM were considered as controls and compared with three other corresponding ASC culture samples, where Ghre (2 ?M) was added. After 1, 3 and 6 days of growth, cells were tested by immunocytochemistry to detect the expression of some neural markers, such as Protein Gene Product (PGP) 9.5, Microtubule Associated Protein (MAP) 2, Glial Fibrillary Acidic Protein (GFAP), Neuron Specific Enolase (NSE). The expression of Ghre and its receptor was also evaluated. Results confirmed that both OEC-CM and SC-CM increased the expression of neural markers in ASCs. These increases, clearly visible already at day 1 and more evident at day 6, were more obvious when Ghre was added, although ASCs treated with Ghre alone exhibited weak modifications. The observed effects are likely due to interactions between Ghre and its receptor, whose expression was also increased. In conclusion, although Ghre alone was not capable of inducing pronounced effects, its addition facilitated neural ASC differentiation. This study highlights the synergic action of Ghre and glial CM on modulation of ASC growth and differentiation.