, 2011). The olfactory system has attracted considerable interest as a promising source of cells for transplantation after SCI, because of its capacity for lifelong regeneration (Lindsay et al., 2010). The main focus of attention in the olfactory tissue has been a unique type of glia, known as the olfactory ensheathing cells (OECs) (Doucette, 1991, Raisman, 2001 and Ramón-Cueto and Muñoz-Quiles, 2011). These cells reside within the two Trametinib in vitro main regions of the olfactory axis: peripherally, in the lamina propria and centrally, along the nerve fiber layer of the olfactory bulb (OB) (Au and Roskams, 2003). The OECs are responsible for maintaining an environment which favors neurite
outgrowth and the creation of new functional synapses
in the central nervous system (Au and Roskams, 2003 and Franssen et al., 2007). Due to their supposed axon regenerative properties, OECs have been extensively studied in animal models of SCI. Although some research has shown locomotor and axonal regeneration improvements, a consensus on the efficacy of this cellular transplantation and mode of action has yet to be reached (Barnett and Riddell, 2007, Boyd et al., 2004, Franssen et al., 2008, Kubasak et al., 2008, Raisman and Li, 2007, Ramón-Cueto and Avila, 1998, Ramón-Cueto et al., 1998, Ramón-Cueto et al., 2000 and Tetzlaff et al., buy ZD1839 2011). The source of OECs for transplantation into injured spinal cord is also subject of debate (Richter et al., 2005). However, the use of olfactory lamina propria (OLP) grafts, which is a more accessible source of OECs in humans, could enable a safer approach for autologous transplantation (Bianco et al., 2004, Féron et al., 1998 and Franklin, 2002). The devastating prognosis associated with the social and economic impacts, has led to increased efforts to find therapies that provide functional recovery for people who undergo severe SCI (Blight, 2002 and van den Berg et al., 2010). According to previous studies, the use of OLP transplantation is a promising, though controversial,
repair strategy (Lu et al., 2001, Lu et al., 2002 and Steward Flavopiridol (Alvocidib) et al., 2006). In the present study we hypothesized that the OECs present in OLP grafts could create a favorable glial environment that would favor neurite and axonal outgrowth after thoracic spinal cord transection in rats. Thus, OLP transplantation could produce higher levels of hindlimb motor recovery when compared to respiratory lamina propria (RLP), which is a graft devoid of OECs. Additionally, we tested the efficacy of OLP transplantation in three different therapeutic windows (acutely, 2 weeks and 4 weeks post-injury), since another key aspect in the translation of this therapy to clinical practice is their potential to produce axonal regeneration even when transplantation is delayed after SCI. Fig.