Olfactory ensheathing cells transplanted in lesioned spinal cord prevent loss of spinal cord parenchyma and promote functional recovery

Abstract

We studied the effects of olfactory ensheathing cells (OECs) transplanted in a photochemical spinal cord injury in adult rats. After dorsal laminectomy at T8 vertebra, subjacent spinal cord was bathed with rose Bengal for 10 min and illuminated with visible light by means of an optic fiber connected to a halogen lamp for 2.5 min at maximal intensity of 8 kLux. Eight injured rats received a suspension of OECs in DMEM, and another eight rats received DMEM alone. Locomotor ability scored by the BBB scale, pain sensibility by the plantar algesimetry test, and motor-and somatosensory-evoked potentials by electrophysiological techniques were evaluated for 3 months postsurgery. Finally, all rats were perfused with paraformaldehyde and transverse sections from the spinal cord segment at the lesion site were immunostained against GFAP. Area of the preserved spinal cord parenchyma was measured from the GFAPimmunolabeled cord sections. The BBB score and the amplitude of motor-and somatosensory-evoked potentials were higher in OECs-transplanted rats than in DMEMinjected animals throughout follow-up, whereas the withdrawal response to heat noxious stimulus was lower in OEC-than in DMEM-injected rats. The area of preserved spinal cord was significantly larger in OECs-transplanted rats than in DMEM-injected animals. These results indicate that OECs promote functional and morphological preservation of the spinal cord after photochemical injury. GLIA 42:275-286, 2003.

Myelination and nodal formation of regenerated peripheral nerve fibers following transplantation of acutely prepared olfactory ensheathing cells

“…Several studies have demonstrated enhanced functional recovery after OEC transplantation into the injured spinal cord (Li et al, 1998;Ramon-Cueto et al, 2000;Plant et al, 2002;Verdu et al, 2003;Sasaki et al, 2004;Garcia-Alias et al, 2005). While the precise mechanism of this functional recovery is not fully understood, several mechanisms have been suggested including remyelination (Devon and Doucette, 1992;Franklin et al, 1996;Imaizumi et al, 1998;Sasaki et al, 2004), long axon tract regeneration (Li et al, 1997;Ramon-Cueto et al, 2000;, axonal sparing (Plant et al, 2002) and plasticity associated with novel polysynaptic pathways (Keyvan-Fouladi et al, 2002;Bareyre et al, 2004).…”

LacZ -expressing olfactory ensheathing cells do not associate with myelinated axons after implantation into the compressed spinal cord

“…This implantation strategy has been associated with increased axonal regeneration and͞or sparing of residual axons (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24), remyelination of axons (25)(26)(27)(28)(29)(30)(31), and improved recovery of locomotor function (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)32).…”

Setting the stage for functional repair of spinal cord injuries: a cast of thousands

“…Recent data suggest that the mechanism of functional return may be more complex than regrowth of lesioned axons. In fact, OEC transplantation protects spinal tissue from secondary damage and prevents cavitation, [241][242][243][244][245][246] enhances vascularization of the lesion site 235,246 and promotes branching of neighboring axons spared by the primary injury, 247 all of which might subserve improved functional outcome. While earlier transplant experiments sought to isolate OECs without other cellular components of the olfactory nerve, recent work suggests that the recovery of function is enhanced by including other cell types, such as olfactory nerve fibroblasts (ONFs), in the graft.…”