The regeneration-enhancing properties of olfactory ensheathing cells in spinal cord injury

One of the newest approaches to creating a growth-permissive environment for axonal regeneration after spinal cord injury (SCI) lies in the use of olfactory ensheathing cells (OECs) as transplant material in the spinal cord. OECs normally provide a permissive environment for regenerating sensory axons in the periphery to extend axons into the olfactory bulb in the adult central nervous system (CNS). It has been shown that OEC transplantation into a rodent SCI significantly enhances functional recovery and long-axon regeneration, through a mechanism attributed to the axonal guidance and neurotrophic properties of these cells. It has been repeatedly demonstrated that the best treatment strategy for SCI will simultaneously target the intrinsic capacity of the neurons to grow and the extrinsic environment of the inhibitory CNS parenchyma. The longterm goal of these studies is to elucidate the best combinatorial treatment strategy for SCI utilizing the regeneration-enhancing properties of OECs.; Previous studies have shown that a treatment combination of testosterone propionate (TP) and a peripheral nerve graft upregulates betaII-tubulin mRNA levels in the injured rubrospinal motoneurons (RSMN) to a greater extent than either treatment alone. In the present studies, several combinatorial treatment strategies and single-therapy strategies for SCI were tested for their ability to upregulate betaII-tubulin mRNA in injured RSMN. All of the single-therapy treatments tested (OECs, brain-derived neurotrophic factor (BDNF), Schwann cells) were able to prevent the drastic downregulation of betaII-tubulin mRNA that occurs in RSMN a week after injury, but the combinatorial treatments (OECs + TP, OECs + BDNF, Schwann cells + TP) actually upregulated levels of betaII-tubulin mRNA expression in injured RSMN.; These studies determined that the best treatment combination for SCI is one that (1) alters the spinal cord environment to more closely resemble that of the growth-permissive peripheral nervous system (i.e. enhance extrinsic factors), (2) triggers axonal growth at the cell body by switching the molecular phenotype to a regenerative state (i.e. improve intrinsic factors), and (3) provides a trophic factor that is able to act on the transplanted material as well as on the regenerating neuron as well.