OLFACTORY ENSHEATHING CELLS AS PROMISING CELL THERAPY TOOL IN CENTRAL NERVOUS SYSTEM INJURY

The olfactory system is characterized by a specialized type of glia, Olfactory Ensheathing Cells (OECs), showing antigenic and morphological features both of astrocytes and Schwann Cells. OECs present some peculiar and interesting aspects as their ability to secrete several Growth Factors (GFs) and capability of intermingling with astrocytes exerting a neuroprotective role by reducing astrocytic gliosis. In addition, they represent a unique population in the olfactory system supporting the continuous neuronal turn-over and sheathing olfactory axons. In vitro, OECs promote axonal growth, in vivo they could form myelin, promoting remyelination of damaged axons. Recently, OECs have emerged as possible supportive cells for regeneration and functional recovery of damaged Central Nervous System (CNS). In fact, they have been the subject of many studies for cellular transplantations in the treatment of neurodegenerative disorders. In this in vitro study we investigated on OEC potential for regeneration and functional recovery in injured CNS. To analyse their antigen modulation, OECs, prepared from postnatal mouse olfactory bulbs, were grown in different culture conditions: standard or serum-free media with/without GFs. A characterization was performed both by flow cytometry and immunocytochemistry for neural specific markers, such as Vimentin, S-100?, Nestin, Glial Fibrillary Acidic Protein, Myelin, Neural Cell Adhesion Molecule, Low-affinity Nerve Growth Factor Receptor p75, Microtubule Associated Protein-2 and Protein Gene Product 9.5. Moreover, the resistance of OECs to the neurotoxin 6-hydroxydopamine (6-OHDA) was analysed by evaluating apoptosis and death. OEC neuroprotective properties were investigated by in vitro co-cultures or by addition of OEC conditioned medium to the neuroblastoma SH-SY5Y cells exposed to 6-OHDA. We observed: 1) modification of OEC morphology, reduced cell growth and marker expression in serum-free medium; 2) GF addition to serum-free medium condition, positively influenced cell growth and restored basal marker expression; 3) an OEC neuroprotective effect, albeit non statistically significant, on 6-OHDA treated SH-SY5Y cells. Therefore, OECs could be expanded in vitro without serum for clinical purpose with only addition of GFs. These peculiar properties of OECs might render them a suitable tool in cellular therapy for their exceptional ability to promote axonal regeneration and functional restoration in different neurological disorders or injured CNS.