IDENTIFICATION OF PECULIAR PHENOTYPIC AND METABOLIC CHARACTERISTICS IN OLFACTORY ENSHEATHING CELLS: A PROMISING TOOL FOR CELL THERAPY.

Olfactory Ensheathing Cells (OECs) show a peculiar plasticity as well as exhibit antigenic and morphological characteristics of both astrocytes and Schwann Cells. In vitro, OECs promote axonal growth and in vivo they can form myelin, promoting remyelination of damaged axons. Therefore, OECs have emerged as possible supportive cells for regeneration and functional recovery in neurodegenerative disorders. We previously demonstrated the functional characterizations and expression/modulation of some markers, such as Vimentin, S-100?, Nestin, Glial Fibrillary Acidic Protein, on OECs grown in different culture conditions: standard or serum-free media with/without Growth Factors (GFs). We observed a change of OEC usual morphology, reduction of cell viability and marker expression in serum-free medium. In addition, a positive influence of GFs on both viability and marker expression was observed. Since cell metabolism is a key determinant factor for the pluripotency and fate commitment of stem/progenitor cells during development, ageing, pathological onset and progression, we also described for the very first time the metabolic fingerprint of OECs. To identify and quantify metabolites, OEC lysates were analysed by proton Nuclear Magnetic Resonance (1H-NMR) spectroscopy coupled to multivariate analysis. This approach revealed that OECs contain high levels of Lactate (39.9%), Acetate (22.3%) and Alanine (15.5%). These latter two metabolites are generally related to stem features whereas highest Lactate levels in OECs may be a reservoir for neuronal energy supply, essential to contrast imbalanced cell metabolism during neurodegneration. Therefore, we demonstrate that the precise metabolites' content defines the function and identity, thus allowing an integrated bioengineering approach for univocal biologic fingerprints able to dissect the cell molecular specificities. In conclusion, our detailed characterization demonstrates the plasticity and specific metabolic peculiarities of OECs, which can be exploited in the treatment of neurodegenerative diseases.