One of the main challenges in neuroscience is that the central nervous system (brain and spinal cord) is virtually unable to regenerate after injury. One factor contributing to this lack of repair is the accumulation of cells and myelin fragments at the site of injury. Fragments cannot be effectively engulfed and can persist for years after initial injury, leading to inflammation inhibiting axonal regeneration. The main cells responsible for phagocytosis in the central nervous system are microglia and astrocytes. Although both types of cells are capable phagocytes, their ability to clear fragments of cells and myelin sheaths is weakened in central nervous system lesions. Unlike the central nervous system, the peripheral nervous system can regenerate unless the damage is complex or large. This is partly due to the ability of peripheral glial cells to rapidly engulf debris after injury, followed by the regulation of inflammation and the secretion of growth factors that support axon growth. The ability to promote regeneration has led to the use of peripheral glial in transplant treatments to treat central nervous system injuries, particularly spinal cord injuries. These peripheral glial cells are Schwann cells and olfactory sheath cells. While these glial cells have many similarities, there are also distinct differences. For example, a comparison of the transcriptomes of Schwann cells and olfactory sheath cells showed that olfactory sheath cells expressed higher levels of factors associated with tissue repair than Sherwan cells, including factors involved in phagocytosis and degradation. Understanding these differences can help guide and improve transplant treatment of the central nervous system. Although peripheral nerve damage rarely occurs, when they do, Sherwan cells engulf debris produced by myelin sheaths and/or necrotic cells by transforming into a repair phenotype. Schwann cells are the first reactive cells after peripheral nerve injury, clearing debris; specialized phagocytes such as macrophages and neutrophils are needed after larger injuries. After the Sherwan cells release pro-inflammatory cytokines and chemokines, these additional phagocytes are recruited to the site of injury.
The team of Jenny Ekberg from Griffith University in Australia believes that the olfactory nerve is different from other peripheral nerves, and the olfactory nerve is constantly regenerated throughout the life process due to the constant renewal of sensory olfactory neurons. Damage or infection of the olfactory nerve can lead to an increase in the number of debris, caused by damaged neurons/axons and other necrotic cells (non-programmed cell death). Similar to Sherwan cells, olfactory sheath cells can also engulf cell debris. Unlike Schwann cells, olfactory sheath cells continue to phagorate debris and do not recruit macrophages. Olfactory sheath cells are the main phagocytes of the olfactory nerve. Both olfactory sheath cells and Schwann cells are effective phagocytes of necrotic bodies, and there are important differences between the two cell types. Olfactory sheath cells can engulf a large number of necrotic bodies and myelin fragments, which degrades necrotic bodies faster than Sherwan cells. Olfactory sheath cells do not produce pro-inflammatory cytokines during this process, while Sherwan cells produce pro-inflammatory cytokines; olfactory sheath cells do not appear to attract macrophages. Overall, olfactory sheath cells are more effective phagocytes that cause less inflammation and are therefore better suited for transplantation into the damaged central nervous system than Sherwan cells. Transplantation of olfactory sheath cells to repair central nervous system damage can help clear necrotic bodies and prevent pro-inflammatory macrophages/microglia from gathering towards the site of injury. To improve treatment outcomes, it is also important to further identify the cellular and molecular mechanisms involved in this process, especially when glial cells are transplanted into sites of pro-inflammatory central nervous system injury. Understanding cellular and molecular mechanisms also helps to discover new drugs that can be used to stimulate the phagocytic activity of olfactory sheath cells and Schwann cells, further enhancing their therapeutic potential.
The article was published in the February 2, 2021 issue of the Journal of Chinese Neurogenesis Research.
文章来源：Nazareth L, St John J, Ekberg J (2022) Improving cell transplantation by understanding and manipulating the phagocytic activity of peripheral glia. Neural Regen Res 17(2):313-314.