Potential therapeutic effect of olfactory ensheathing cells in neurological diseases: neurodegenerative diseases and peripheral nerve injuries.

Neurological diseases are destructive, mainly characterized by the failure of endogenous repair, the inability to recover tissue damage, resulting in the increasing loss of cognitive and physical function. Although some clinical drugs can alleviate the progression of these diseases, but they lack therapeutic effect in repairing tissue injury and rebuilding neurological function. More and more studies have shown that cell therapy has made good achievements in the application of nerve injury. Olfactory ensheathing cells (OECs) are a special type of glial cells, which have been proved to play an important role as an alternative therapy for neurological diseases, opening up a new way for the treatment of neurological problems. The functional mechanisms of OECs in the treatment of neurological diseases include neuroprotection, immune regulation, axon regeneration, improvement of nerve injury microenvironment and myelin regeneration, which also include secreted bioactive factors. Therefore, it is of great significance to better understand the mechanism of OECs promoting functional improvement, and to recognize the implementation of these treatments and the effective simulation of nerve injury disorders. In this review, we discuss the function of OECs and their application value in the treatment of neurological diseases, and position OECs as a potential candidate strategy for the treatment of nervous system diseases.

Zhang LP ，Liao JX ，Liu YY ，Luo HL ，Zhang WJ ... -  《Frontiers in Immunology》

Application of olfactory ensheathing cells in peripheral nerve injury and its complication with pathological pain.

Ding L ，Hu DX ，Yang L ，Zhang WJ ... -  《-》

Olfactory-ensheathing cell transplantation for peripheral nerve repair: update on recent developments.

A number of important advances have been made using transplantation of olfactory-ensheathing cells (OECs) to provide therapeutic effects with regard to peripheral nerve repair. In vivo studies have focused on transplanting OECs to stimulate axonal regeneration and sprouting, increase remyelination, confer neuroprotection, enhance neovascularization and replace lost cells. OECs support axonal regeneration and remyelination with appropriate formation of axonal nodes of Ranvier with improvement of nerve conduction velocity. Current work using gene profiling and proteomics is identifying potential therapeutic differences between OECs harvested from nasal mucosa and the olfactory bulb and genes that OECs express that may be conducive to neural repair. OECs derived from nasal mucosa are of clinical interest since the cells could potentially be harvested from a patient and used for autotransplantation. Various nerve scaffolds and materials have been used for nerve repair and recent studies have examined OECs in combination with various supportive materials, including nanoparticles and scaffolds for peripheral nerve substance defects. This review will discuss the use of OECs in nerve repair and nerve defect injuries with specific emphasis on differences between OECs derived from the olfactory bulb and the olfactory mucosa.

Radtke C ，Kocsis JD 《-》

Olfactory Ensheathing Cell Transplantation after a Complete Spinal Cord Transection Mediates Neuroprotective and Immunomodulatory Mechanisms to Facilitate Regeneration.

Multiple neural and peripheral cell types rapidly respond to tissue damage after spinal cord injury to form a structurally and chemically inhibitory scar that limits axon regeneration. Astrocytes form an astroglial scar and produce chondroitin sulfate proteoglycans (CSPGs), activate microglia, and recruit blood-derived immune cells to the lesion for debris removal. One beneficial therapy, olfactory ensheathing cell (OEC) transplantation, results in functional improvements and promotes axon regeneration after spinal cord injury. The lack of an OEC-specific marker, however, has limited the investigation of mechanisms underlying their proregenerative effects. We compared the effects of enhanced green fluorescent protein-labeled fibroblast (FB) and OEC transplants acutely after a complete low-thoracic spinal cord transection in adult rats. We assessed the preservation of neurons and serotonergic axons, the levels of inhibitory CSPGs and myelin debris, and the extent of immune cell activation between 1 and 8 weeks postinjury. Our findings indicate that OECs survive longer than FBs post-transplantation, preserve axons and neurons, and reduce inhibitory molecules in the lesion core. Additionally, we show that OECs limit immune-cell activation and infiltration, whereas FBs alter astroglial scar formation and increase immune-cell infiltration and concomitant secondary tissue damage. Administration of cyclosporine-A to enhance graft survival demonstrated that immune suppression can augment OEC contact-mediated protection of axons and neurons during the first 2 weeks postinjury. Collectively, these data suggest that OECs have neuroprotective and immunomodulatory mechanisms that create a supportive environment for neuronal survival and axon regeneration after spinal cord injury. Spinal cord injury creates physical and chemical barriers to axon regeneration. We used a complete spinal cord transection model and olfactory ensheathing cell (OEC) or fibroblast (FB; control) transplantation as a repair strategy. OECs, but not FBs, intermingled with astrocytes, facilitated astroglial scar border formation and sequestered invading peripheral cells. OECs attenuated immune cell infiltration, reduced secondary tissue damage, protected neurons and axons in the lesion core, and helped clear myelin debris. Immunosuppression enhanced survival of OECs and FBs, but only OEC transplantation promoted scaffold formation in the lesion site that facilitated axon regeneration and neuron preservation.

Khankan RR ，Griffis KG ，Haggerty-Skeans JR ，Zhong H ，Roy RR ，Edgerton VR ，Phelps PE ... -  《-》

Understanding the neural repair-promoting properties of olfactory ensheathing cells.

Olfactory ensheathing glial cells (OECs) are a specialized type of glia that form a continuously aligned cellular pathway that actively supports unprecedented regeneration of primary olfactory axons from the periphery into the central nervous system. Implantation of OECs stimulates neural repair in experimental models of spinal cord, brain and peripheral nerve injury and delays disease progression in animal models for neurodegenerative diseases like amyotrophic lateral sclerosis. OECs implanted in the injured spinal cord display a plethora of pro-regenerative effects; they promote axonal regeneration, reorganize the glial scar, remyelinate axons, stimulate blood vessel formation, have phagocytic properties and modulate the immune response. Recently genome wide transcriptional profiling and proteomics analysis combined with classical or larger scale "medium-throughput" bioassays have provided novel insights into the molecular mechanism that endow OECs with their pro-regenerative properties. Here we review these studies and show that the gaps that existed in our understanding of the molecular basis of the reparative properties of OECs are narrowing. OECs express functionally connected sets of genes that can be linked to at least 10 distinct processes directly relevant to neural repair. The data indicate that OECs exhibit a range of synergistic cellular activities, including active and passive stimulation of axon regeneration (by secretion of growth factors, axon guidance molecules and basement membrane components) and critical aspects of tissue repair (by structural remodeling and support, modulation of the immune system, enhancement of neurotrophic and antigenic stimuli and by metabolizing toxic macromolecules). Future experimentation will have to further explore the newly acquired knowledge to enhance the therapeutic potential of OECs.

Roet KC ，Verhaagen J 《-》