Effects of ensheathing cells transplanted into photochemically damaged spinal cord

Abstract

Transplantation of olfactory ensheathing cells (OECs) into photochemically damaged rat spinal cord diminished astrocyte reactivity and parenchyma cavitation. The photochemical lesion performed at T12--L1 resulted in severe damage to the spinal cord, so that during the first 15 days postoperation all rats dragged their hindlimbs and did not respond to pinprick. The maximal area and volume of the cystic cavities were lower in transplanted than in non-transplanted rats, not significantly at the T12--L1 lesion site, but significantly at T9--T10 and L4--L6 cord levels. The density of astrocytes in the grey matter was similar at T12--L1 and L4--L6 in non-transplanted and trans- planted rats, but lower in the latter at T9--T10 level. However, in non-transplanted rats all astrocytes showed a hypertrophied appearance, with long and robust processes heavily GFAP-positive, and overexpression of proteoglycan inhibitor of neuritogenesis, whereas in transplanted rats only a few astrocytes showed hypertrophy and the majority had short, thin processes. These results indicate that OECs transplanted into damaged adult rat spinal cord exert a neuroprotective role by reducing astrocytic gliosis and cystic cavitation.

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

“…Secondly, OECs transplanted in lesioned spinal cords induce a downregulation of GFAP and proteoglycan expression by the reactive astrocytes (Verdú et al, 2001). In the present study, we confirm these results at a longer time, 3 months postlesion, when the injury process has reached a steady state.…”

“…In previous studies, we reported that during the first 60 min posttrauma, light and electron microscopy showed an important cytotoxic edema with astrocytic swelling, hemorrhagic extravasation, and myelin degradation in the lesion site. After 15 days, a cavity was observed in the necrotic area, and hypertrophied, heavily GFAP-and proteoglycan-stained astrocytes were seen delimiting this cavity (Verdú et al, 2001. A photochemical lesion in adult rats can induce graded severity of spinal cord injury.…”

“…Another eight rats received four injections of an equal volume of vehicle alone (group DMEM). The suspension was applied through a glass micropipette by means of repeated 20-ms pulses of 10 psi (Picospitzer II, General Valve, Fairfield, NJ) (Verdú et al, 2001). Finally, the wound was closed and the animals were kept in a warm environment until full recovery.…”

“…These findings clearly demonstrate that OECs might be used for promoting axonal regeneration and functional recovery after a severe spinal cord injury. In a previous study, we reported that, after severe photochemical cord injury, OECs-transplanted rats showed significantly lower area of cystic cavity and lower expression of proteoglycan and glial fibrillary acidic protein (GFAP) by reactive astrocytes in comparison with nontransplanted animals (Verdú et al, 2001). In vitro studies also demonstrated that OECs modulate GFAP and proteoglycan expression in reactive astrocytes (Lakatos et al, 2000(Lakatos et al, , 2002.…”

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.…”