Reliable cell purification and determination of cell purity:crucial aspects of olfactory ensheathing cell transplantation for spinal cord repair

Transplantation of olfactory ensheathing cells,the glia of the primary olfactory nervous system,has been trialed for spinal cord injury repair with promising but variable outcomes in animals and humans.Olfactory ensheathing cells can be harvested either from the lamina propria beneath the neuroepithelium in the nasal cavity,or from the olfactory bulb in the brain.As these areas contain several other cell types,isolating and purifying olfactory ensheathing cells is a critical part of the process.It is largely unknown how contaminating cells such as fibroblasts,other glial cell types and supporting cells affect olfactory ensheathing cell function post-transplantation;these cells may also cause unwanted side-effects.It is also,however,possible that the presence of some of the contaminant cells can improve outcomes.Here,we reviewed the last decade of olfactory ensheathing cell transplantation studies in rodents,with a focus on olfactory ensheathing cell purity.We analyzed how purification methods and resultant cell purity differed between olfactory mucosa-and olfactory bulb-derived cell preparations.We analyzed how the studies reported on olfactory ensheathing cell purity and which criteria were used to define cells as olfactory ensheathing cells.Finally,we analyzed the correlation between cell purity and transplantation outcomes.We found that olfactory bulb-derived olfactory ensheathing cell preparations are typically purer than mucosa-derived preparations.We concluded that there is an association between high olfactory ensheathing cell purity and favourable outcomes,but the lack of olfactory ensheathing cell-specific markers severely hampers the field.

Olfactory ensheathing cells for spinal cord repair: crucial differences between subpopulations of the glia

OECs for spinal cord repair： Is repairing the iniured spinal cord by olfactory ensheathing cell （OEC） transplantation pos- sible？ A recent human trial in which a paralysed man regained some function after transplantation of partially purified OECs suggests that this therapy may be a successful approach （Ta- bakow et al., 2014）. In another human trial in which olfactory mucosa lamina propria was transplanted, patients recovered some motor and sensory function （Wang et al., 2015）. While these results show promise, it is clear that improvements are needed to provide patients with increased functional output. Strategies to improve the therapeutic use of OECs may include improving the purification of the OECs used for transplantation, using them in combination with growth factors to combat the inhibitory environment and improve anon growth, the use of nerve bridges, advanced physiotherapy and the use of exo- skeleton robotics to reinforce functional connections. Of all these approaches, it is probably is primarily addressed to ensure crucial that the purity of OECs consistency in outcomes.

Neuron-fibrous scaffold interfaces in the peripheral nervous system: a perspective on the structural requirements

The nerves of the peripheral nervous system are not able to effectively regenerate in cases of severe neural injury.This can result in debilitating consequences,including morbidity and lifelong impairments affecting the quality of the patient’s life.Recent findings in neural tissue engineering have opened promising avenues to apply fibrous tissue-engineered scaffolds to promote tissue regeneration and functional recovery.These scaffolds,known as neural scaffolds,are able to improve neural regeneration by playing two major roles,namely,by being a carrier for transplanted peripheral nervous system cells or biological cues and by providing structural support to direct growing nerve fibers towards the target area.However,successful implementation of scaffold-based therapeutic approaches calls for an appropriate design of the neural scaffold structure that is capable of up-and down-regulation of neuron-scaffold interactions in the extracellular matrix environment.This review discusses the main challenges that need to be addressed to develop and apply fibrous tissue-engineered scaffolds in clinical practice.It describes some promising solutions that,so far,have shown to promote neural cell adhesion and growth and a potential to repair peripheral nervous system injuries.

Radial glia interact with primary olfactory axons to regulate development of the olfactory bulb

The developing olfactory system - merging of the periph- eral and central nervous systems： The olfactory system is responsible for the sense of smell and is comprised of a complex topographic map that regenerates throughout life. In rodents each olfactory sensory neuron expresses one of N 1,300 odorant receptors with the neurons being distributed mosaically within the epithelium. The axons of the sensory neurons do not maintain near-neighbour relationships and instead project to disparate topographic targets in the olfac- tory bulb within the central nervous system. The develop- ment of the targets relies on the intermingling of the sensory axons with the interneurons, glia and second order neurons of the olfactory bulb. Thus the formation of the olfactory system involves the coordinated integration of the axons of the peripheral olfactory sensory neurons with the cells of the olfactory bulb.