Olfactory ensheathing cells: Bridging the gap in spinal cord injury

SPINAL CORD INJURY (SCI) continues to be an insidious and challenging probl em for scientists and clinicians. Recent neuroscientific advances have chan ged the pessimistic notion that axons are not capable of significant extens ion after transection. The challenges of recovering from SCI have been broa dly divided into four areas: 1) cell survival; 2) axon regeneration (growth ); 3) correct targeting by growing axons; and 4) establishment of correct a nd functional synaptic appositions. After acute SCI, there seems to be a th erapeutic window of opportunity within which the devastating consequences o f the secondary injury can be ameliorated. This is supported by several obs ervations in which apoptotic glial cells have been identified up to 1 week after acute SCI. Moreover, autopsy studies have identified anatomically pre served but unmyelinated axons that could potentially subserve normal physio logical properties. These observations suggest that therapeutic strategies after SCI can be directed into two broad modalities: 1) prevention or ameli oration of the secondary injury, and 2) restorative or regenerative interve ntions. Intraspinal transplants have been used after SCI as a means for res toring the severed neuraxis. Fetal cell transplants and, more recently, pro genitor cells have been used to restore intraspinal circuitry or to serve a s relay for damaged axons. In an attempt to remyelinate anatomically preser ved but physiologically disrupted axons, newer therapeutic interventions ha ve incorporated the transplantation of myelinating cells, such as Schwann c ells, oligodendrocytes, and olfactory ensheathing cells. Of these cells, th e olfactory ensheathing cells have become a more favorable candidate for ex tensive remyelination and axonal regeneration. Olfactory ensheathing cells are found along the full length of the olfactory nerve, from the basal lami na of the epithelium to the olfactory bulb, crossing the peripheral nervous system-central nervous system junction. In vitro, these cells promote robu st axonal growth, in part through cell adhesion molecules and possibly by s ecretion of neurotrophic growth factors that support axonal elongation and extension. In animal models of SCI, transplantation of ensheathing cells su pports axonal remyelination and extensive migration throughout the length o f the spinal cord. Although the specific properties of these cells that gov ern enhanced axon regeneration remain to be elucidated, it seems certain th at they will contribute to the establishment of new horizons in SCI researc h.