中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2022, Vol. 17 ›› Issue (2): 313-314.doi: 10.4103/1673-5374.317969

• 观点:神经损伤修复保护与再生 • 上一篇    下一篇

通过了解和操纵外周胶质细胞的吞噬活性来改善细胞移植

  

  • 出版日期:2022-02-15 发布日期:2021-10-08

Improving cell transplantation by understanding and manipulating the phagocytic activity of peripheral glia

Lynn Nazareth, James St John, Jenny Ekberg*   

  1. Menzies Health Institute Queensland, Griffith University, Southport, Australia (Nazareth L, 
    St John J, Ekberg J)
    Clem Jones Centre for Neurobiology and Stem Cell Research, Griffith University, Nathan, Australia (Nazareth L, St John J, Ekberg J)
    Griffith Institute for Drug Discovery, Griffith University, Nathan, Australia (St John J, Ekberg J)
  • Online:2022-02-15 Published:2021-10-08
  • Contact: Jenny Ekberg, PhD, j.ekberg@griffith.edu.au.
  • Supported by:
    This work was supported by a Garnett-Passe and Rodney Williams Memorial Foundation Grant to JE, a National Health and Medical Research Council Grant to JS and JE (grant No. APP1183799), a Motor Accident Insurance Commission Queensland Grant to JS and JE, a Perry Cross Foundation Grant to JE and JS, and a Clem Jones Foundation grant to JS and JE.  

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摘要： Neural Regen Res：雪旺细胞和嗅鞘细胞对坏死体的吞噬反应：改善细胞移植效果
神经科学的主要挑战之一是中枢神经系统（大脑和脊髓）在受伤后基本上无法再生。造成这种缺乏修复的一个因素是损伤部位细胞和髓鞘碎片的积聚。碎片不能被有效地吞噬，并且在初始损伤后可以持续数年，导致炎症抑制轴突再生。中枢神经系统中负责吞噬的主要细胞是小胶质细胞和星形胶质细胞。虽然这两种细胞都是有能力的吞噬细胞，但它们清除细胞和髓鞘碎片的能力在中枢神经系统病变中减弱。与中枢神经系统不同的是，周围神经系统可以再生，除非损伤很复杂或很大。这部分是由于外周胶质细胞在损伤后快速吞噬碎片的能力，然后是炎症的调节和支持轴突生长的生长因子的分泌。促进再生的能力导致了在移植治疗中使用外周神经胶质来治疗中枢神经系统损伤，特别是脊髓损伤。这些周围神经胶质细胞是雪旺氏细胞和嗅鞘细胞。虽然这些胶质细胞有许多相似之处，但也有明显的区别。例如，对雪旺细胞和嗅鞘细胞转录组的比较表明，嗅鞘细胞表达的与组织修复相关的因子水平高于雪旺细胞，包括参与吞噬和降解的因子。了解这些差异有助于指导和改进中枢神经系统的移植治疗。虽然周围神经损伤很少发生，但当它们发生时，雪旺细胞通过转化为修复表型来吞噬髓鞘和/或坏死细胞产生的碎片。雪旺细胞是外周神经损伤后的第一反应细胞，清除碎片；在较大损伤后需要巨噬细胞和中性粒细胞等专业吞噬细胞。雪旺细胞释放促炎细胞因子和趋化因子后，这些额外的吞噬细胞被招募到损伤部位。
来自澳大利亚格里菲斯大学的Jenny Ekberg团队认为，嗅觉神经不同于其他周围神经，由于感觉嗅觉神经元的不断更新，嗅觉神经在整个生命过程中不断再生。嗅觉神经的损伤或感染可导致碎片数量增加，是由于受损的神经元/轴突和其他正在坏死的细胞（非程序性细胞死亡）引起的。与雪旺细胞相似，嗅鞘细胞也能吞噬细胞碎片。与雪旺细胞不同的是，嗅鞘细胞持续吞噬碎片，并且不招募巨噬细胞。嗅鞘细胞是嗅觉神经的主要吞噬细胞。嗅鞘细胞和雪旺细胞都是坏死小体的有效吞噬细胞，两种细胞类型之间有着重要的区别。嗅鞘细胞能吞噬大量坏死小体和髓鞘碎片，比雪旺细胞降解坏死小体更快。嗅鞘细胞在此过程中不产生促炎细胞因子，而雪旺细胞产生促炎细胞因子；嗅鞘细胞似乎不吸引巨噬细胞。总的来说，嗅鞘细胞是更有效的吞噬细胞，引起的炎症更少，因此比雪旺细胞更适合移植到受损的中枢神经系统。移植嗅鞘细胞修复中枢神经系统损伤可有助于坏死体的清除，并阻止促炎性巨噬细胞/小胶质细胞向损伤部位聚集。为了改善治疗效果，进一步确定参与这一过程的细胞和分子机制也很重要，特别是当胶质细胞被移植到促炎中枢神经系统损伤部位中时。了解细胞和分子机制也有助于发现新的药物，可用于刺激嗅鞘细胞和雪旺细胞的吞噬活性，进一步提高其治疗潜力。

    文章在《中国神经再生研究（英文版）》杂志2021年 2 月 2 期发表。

https://orcid.org/0000-0001-5151-4966 (Jenny Ekberg) 

Abstract: One of the key challenges in neuroscience is that the central nervous system (CNS; the brain and spinal cord), is largely unable to regenerate after injury. One factor contributing to this lack of repair is the accumulation of cellular and myelin debris at the site of injury. The debris is not efficiently phagocytosed and can persist for years after the initial injury, resulting in an inflammatory environment which inhibits axonal regrowth (Lutz and Barres, 2014). The main cells responsible for phagocytosis in the CNS are microglia and astrocytes. While both these cells are competent phagocytes, their ability to clear cellular and myelin debris is diminished in CNS pathologies (Lutz and Barres, 2014). In contrast to the CNS, the peripheral nervous system can regenerate unless the injury is complex or large. This is partly due to the ability of peripheral glia to rapidly phagocytose debris after an injury, followed by modulation of inflammation and secretion of growth factors that support axonal growth (Barton et al., 2017). The ability to promote regeneration has led to the use of peripheral glia in transplantation therapies to treat CNS injuries, particularly spinal cord injury. These peripheral glia are (1) Schwann cells, which surround most peripheral nerves and (2) olfactory ensheathing cells (OECs), which are the glia of the olfactory nerve. While these glia share many similarities, there have distinct differences. For example, a comparison of the Schwann cell and OEC transcriptomes showed that OECs express higher levels of factors relating to tissue repair than Schwann cells, including those involved in phagocytosis and degradation (Franssen et al., 2008). Understanding these differences may guide and improve transplantation therapies to repair the CNS.