Differing phagocytic capacities of accessory and main olfactory ensheathing cells and the implication for olfactory glia transplantation therapies

Abstract

The rodent olfactory systems comprise the main olfactory system for the detection of odours and the accessory olfactory system which detects pheromones. In both systems, olfactory axon fascicles are ensheathed by olfactory glia, termed olfactory ensheathing cells (OECs), which are crucial for the growth and maintenance of the olfactory nerve. The growth-promoting and phagocytic characteristics of OECs make them potential candidates for neural repair therapies such as transplantation to repair the injured spinal cord. However, transplanting mixed populations of glia with unknown properties may lead to variations in outcomes for neural repair. As the phagocytic capacity of the accessory OECs has not yet been determined, we compared the phagocytic capacity of accessory and main OECs in vivo and in vitro. In normal healthy animals, the accessory OECs accumulated considerably less axon debris than main OECs in vivo. Analysis of freshly dissected OECs showed that accessory OECs contained 20% less fluorescent axon debris than main OECs. However, when assayed in vitro with exogenous axon debris added to the culture, the accessory OECs phagocytosed almost 20% more debris than main OECs. After surgical removal of one olfactory bulb which induced the degradation of main and accessory olfactory sensory axons, the accessory OECs responded by phagocytosing the axon debris. We conclude that while accessory OECs have the capacity to phagocytose axon debris, there are distinct differences in their phagocytic capacity compared to main OECs. These distinct differences may be of importance when preparing OECs for neural transplant repair therapies.

Stem‐cell–based therapies to enhance peripheral nerve regeneration

“…This cell class originates as the myelinating cell of the olfactory bulb in fetal development. 114 Olfactory ensheathing cells (OECs) have demonstrated an ability to respond to injury by secretion of an extensive array of neurotrophins, 115 and also act as the primary phagocytic cell of the olfactory bulb, 116 clearing debris and bacteria alike. 117 OECs have shown great promise in restoring function and improving histological injury parameters in animal models of spinal cord injury, [118][119][120][121][122] and they remain one of the few cell types to be utilized experimentally in clinical human spinal cord injury.…”

The Glia Response after Peripheral Nerve Injury: A Comparison between Schwann Cells and Olfactory Ensheathing Cells and Their Uses for Neural Regenerative Therapies

“…Instead, OECs are the primary immune cells of the olfactory nerve, responsible for clearing both the axonal debris resulting from the olfactory nerve turnover and invading microorganisms [4]. Olfactory neuron dendrites extend directly into the nasal cavity and are constantly exposed to microorganisms, and thus, OECs are considered crucial for protecting the CNS from microbial invasion via the olfactory nerve [4,22,23]. OECs are not one uniform population of cells; there are at least five subpopulations with distinct functions and anatomical locations [24].…”

“…After experimental peripheral injury to the olfactory epithelium with zinc sulphate or methimazole, OECs also migrate towards the bulb, undergo morphological changes and increase their level of phagocytosis [4,22,43]. One study, however, showed that OECs did not proliferate or migrate after olfactory nerve axotomy, but instead maintained open channels through which new axons could extend [44], suggesting that the behaviour of OECs is adaptable to the type of nerve injury.…”

“…Macrophages are largely absent from this nerve, and are not in direct contact with axon fascicles. Instead, it is OECs that continuously clear the debris [22]. As discussed earlier, OECs have been identified as the primary innate immunocyte of the olfactory nervous system [45].…”

“…As discussed earlier, OECs have been identified as the primary innate immunocyte of the olfactory nervous system [45]. Even after olfactory nerve injury, OECs are the main cells responsible for debris clearance, and macrophage recruitment to the area is very limited [22]. …”