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Olfactory ensheathing cells (OECs) are glia reported to sustain the continuous axon extension and successful topographic targeting of the olfactory receptor neurons responsible for the sense of smell (olfaction). Due to this distinctive property, OECs have been trialed in human cell transplant therapies to assist in the repair of central nervous system injuries, particularly those of the spinal cord. Though many studies have reported neurological improvement, the therapy remains inconsistent and requires further improvement. Much of this variability stems from differing olfactory cell populations prior to transplantation into the injury site. While some studies have used purified cells, others have used unpurified transplants. Although both preparations have merits and faults, the latter increases the variability between transplants received by recipients. Without a robust purification procedure in OEC transplantation therapies, the full potential of OECs for spinal cord injury may not be realised.

Recent results have shown that nature’s water splitting catalyst inserts an additional water molecule into what appears to be a solvent inaccessible site late in its reaction cycle. The emerging consensus of the field is that this water molecule is one of the substrates of the reaction. Here, we show that this water molecule does not come directly from solvent. It instead represents an earlier bound water, which is inserted into this site via facile structural tautomerism. The trigger for this process is cofactor oxidation. This then allows an additional water to bind from solvent to a more open site of the cofactor. In this way the cofactor carefully regulates water uptake, preventing water insertion earlier in the reaction cycle. Nature’s water splitting cofactor passes through a series of catalytic intermediates (S 0 -S 4 ) before O-O bond formation and O 2 release. In the second last transition (S 2 to S 3 ) cofactor oxidation is coupled to water molecule binding to Mn1. It is this activated, water-enriched all Mn IV form of the cofactor that goes on to form the O-O bond, after the next light-induced oxidation to S 4 . How cofactor activation proceeds remains an open question. Here, we report a so far not described intermediate (S 3 ') in which cofactor oxidation has occurred without water insertion. This intermediate can be trapped in a significant fraction of centers (>50%) in ( i ) chemical-modified cofactors in which Ca 2+ is exchanged with Sr 2+ ; the Mn 4 O 5 Sr cofactor remains active, but the S 2 -S 3 and S 3 -S 0 transitions are slower than for the Mn 4 O 5 Ca cofactor; and ( ii ) upon addition of 3% vol/vol methanol; methanol is thought to act as a substrate water analog. The S 3 ' electron paramagnetic resonance (EPR) signal is significantly broader than the untreated S 3 signal (2.5 T vs. 1.5 T), indicating the cofactor still contains a 5-coordinate Mn ion, as seen in the preceding S 2 state. Magnetic double resonance data extend these findings revealing the electronic connectivity of the S 3 ' cofactor is similar to the high spin form of the preceding S 2 state, which contains a cuboidal Mn 3 O 4 Ca unit tethered to an external, 5-coordinate Mn ion (Mn4). These results demonstrate that cofactor oxidation regulates water molecule insertion via binding to Mn4. The interaction of ammonia with the cofactor is also discussed.

Accumulating evidence sustains glial cells as critical players during central nervous system (CNS) development, homeostasis and disease. Olfactory ensheathing cells (OECs), a type of specialized glia cells sharing properties with both Schwann cells and astrocytes, are of critical importance in physiological condition during olfactory system development, supporting its regenerative potential throughout the adult life. These characteristics prompted research in the field of cell-based therapy to test OEC grafts in damaged CNS. Neuroprotective mechanisms exerted by OEC grafts are not limited to axonal regeneration and cell differentiation. Indeed, OEC immunomodulatory properties and their phagocytic potential encourage OEC-based approaches for tissue regeneration in case of CNS injury. Herein we reviewed recent advances on the immune role of OECs, their ability to modulate CNS microenvironment via bystander effects and the potential of OECs as a cell-based strategy for tissue regeneration.

Olfactory ensheathing cell (OEC) transplantation is emerging as a promising treatment option for injuries of the nervous system. OECs can be obtained relatively easily from nasal biopsies, and exhibit several properties such as secretion of trophic factors, and phagocytosis of debris that facilitate neural regeneration and repair. But a major limitation of OEC-based cell therapies is the poor survival of transplanted cells which subsequently limit their therapeutic efficacy. There is an unmet need for approaches that enable the in vitro production of OECs in a state that will optimize their survival and integration after transplantation into the hostile injury site. Here, we present an overview of the strategies to modulate OECs focusing on oxygen levels, stimulating migratory, phagocytic, and secretory properties, and on bioengineering a suitable environment in vitro.

Spinal cord injury (SCI) is a devastating type of neurological disorder of the central nervous system (CNS) with high mortality and disability. The pathological processes of SCI can usually be described as two stages, namely, primary and acute secondary injuries. Secondary injury produces more significant exacerbations of the initial injury. Among all the mechanisms of secondary damage, infection and inflammatory responses, as the principle culprits in initiating the second phase of SCI, can greatly contribute to the severity of SCI and numerous sequelae after SCI. Therefore, effectively antagonizing pro-inflammatory responses may be a promising treatment strategy to facilitate functional recovery after SCI. Olfactory ensheathing cells (OECs), a unique type of glial cells, have increasingly become potential candidates for cell-based therapy in the injured CNS. Strikingly, there is growing evidence that the mechanisms underlying the anti-inflammatory role of OECs are associated with the immune properties and secretory functions of these cells responsible for anti-neuroinflammation and immunoregulatory effects, leading to maintenance of the internal microenvironment. Accordingly, a more profound understanding of the mechanism of OEC immunological functions in the treatment of SCI would be beneficial to improve the therapeutic clinical applications of OECs for SCI. In this review, we mainly summarize recent research on the cellular and molecular immune attributes of OECs. The unique biological functions of these cells in promoting neural regeneration are discussed in relation of the development of novel therapies for CNS injury.

Cellular transplantation strategies utilizing intraspinal or intrathecal olfactory ensheathing cells (OECs) have been reported as beneficial for spinal cord injury (SCI). However, there are many disadvantages of these methods, including additional trauma to the spinal cord parenchyma and technical challenges. Therefore, we investigated the feasibility and potential benefits of intravenous transplantation of OECs in a rat hemisection SCI model. OECs derived from olfactory bulb tissue were labeled with quantum dots (QDs), and their biodistribution after intravenous transplantation was tracked using a fluorescence imaging system. Accumulation of the transplanted OECs was observed in the injured spinal cord within 10 min, peaked at seven days after cell transplantation, and decreased gradually thereafter. This time window corresponded to the blood–spinal cord barrier (BSCB) opening time, which was quantitated with the Evans blue leakage assay. Using immunohistochemistry, we examined neuronal growth (GAP-43), remyelination (MBP), and microglia (Iba-1) reactions at the lesion site. Motor function recovery was also measured using a classic open field test (Basso, Beattie and Bresnahan score). Compared with the group injected only with QDs, the rats that received OEC transplantation exhibited a prominent reduction in inflammatory responses, increased neurogenesis and remyelination, and significant improvement in motor function. We suggest that intravenous injection could also be an effective method for delivering OECs and improving functional outcomes after SCI. Moreover, the time course of BSCB disruption provides a clinically relevant therapeutic window for cell-based intervention.

Background: Glaucoma is the leading cause of irreversible blindness, and the loss of retinal ganglion cells (RGCs) is the most important pathological feature. During the progression of glaucoma, glutamate content in the optic nerve increases, and glutamate-induced excitotoxicity will aggregate the damage and death of RGCs. We have previously reported that olfactory ensheathing cells (OECs) transplantation preserved the visual function of the glaucoma model but the mechanism is unknown. Methods: Adult Long-Evans rats were used in the present study and injecting magnetic microspheres was used to establish a glaucoma model in rats. Optokinetic response test and Pattern electroretinogram recording were used to assess the visual functions of rats. RT-PCR, immunofluorescence, and co-culture experiments were performed to investigate the therapeutic effects and mechanisms of OECs for glaucoma. Results: In the glaucoma model, increased glutamate content and the damage of astrocytes (AC) and RGCs were observed. OECs transplantation reduced the glutamate concentration in the optic nerve, alleviated the apoptosis of AC and RGCs, and protected the visual function of the glaucoma model. Furthermore, we found that OECs possessed a stronger capacity to metabolize excessive glutamate compared with AC and Müller glia. OECs could improve the glutamate microenvironment of the optic nerve to prevent AC and RGCs from glutamate-induced excitotoxicity in glaucoma. And the recovery of AC function further supported the survival of RGCs. Conclusions: We demonstrate that OECs transplantation could play a neuroprotective role by regulating the glutamate microenvironment in glaucoma.

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.

The process of nerve injury is accompanied by the change of inflammatory microenvironment, which is not conducive to axonal regeneration and hinders the repair of injured nerve. Therefore, looking for a way to improve the inflammatory attack and immune state around the injured nerve is beneficial to the progress of nerve injury repair. In recent years, cell transplantation strategy has played a foreground role in the repair of nerve injury. Olfactory ensheathing cells (OECs) are a special kind of glial cells, which have the characteristics of continuous renewal and survival, antigenic characteristics, variability and promoting the repair of nerve injury. OECs have been recognized in different injury models, including clinical trials, which has become a dominant cell in cell replacement therapy. An important feature of OECs lies in their anti-inflammatory and immunomodulatory functions. They are transplanted into the host to improve the catastrophic inflammatory microenvironment caused by injured nerves, thus promoting the repair and regeneration of injured nerves. The transplantation of OECs into the host can provide good groundwork and support for the repair and regeneration of nerve injury by regulating the activity and infiltration of immune cells, the secretion of inflammatory cytokines and phagocytosis. Therefore, this paper discusses the anti-inflammatory and immunomodulatory mechanisms of OECs transplantation in the repair of nerve injury and the functional role of OECs as an ideal substitute in the treatment of nerve injury.

This study investigated Environmental Sustainability (ES) and Environmental Performance (EP) through the direct and indirect use of Organizational Environmental Culture (OEC). This study focused on top managers, namely, the CEOs and directors of SMEs, along with their middle managers. In this study, the researchers employed green HRM and Green Innovation (GI) as mediators. We applied a quantitative approach that utilized cross-sectional data collected from Saudi Arabian Small and Medium-sized Enterprises (SMEs). We used a survey questionnaire with a convenience sampling technique and succeeded in obtaining replies from 236 respondents. By using the Structural Equation Model (SEM), this study’s findings demonstrate that OEC has a positive and significant effect on green HRM and GI. This study’s findings support the development of policies that promote ES and EP through green environmental practices. Further, green HRM and GI are significant predictors of ES and EP. This study’s findings also show that green HRM and GI have a mediating effect in developing the associations between OEC and ES and EP. Ultimately, this study’s findings make a significant contribution to the depth of the empirical evidence about SMEs in the context of Saudi Arabia.