脊髓损伤后神经修复过程中的细胞微环境

Cellular microenvironment in nerve repair after spinal cord injury

背景:以往的研究显示单一改变脊髓损伤区域某一基因表达或者某一细胞的状态,对脊髓损伤后功能恢复无显著影响,而大量证据表明调控脊髓损伤后紊乱的细胞微环境是神经功能恢复的关键因素。目的:对脊髓损伤前后细胞微环境的生物学特性,包括多种细胞之间的相互调控以及细胞外组分对损伤神经修复的作用和机制进行综述。方法:由第一作者检索PubMed及Web of Science数据库,英文检索词为“spinal cord injury,glial cell,neuron,immune cell,neural stem cell,extracellular matrix,cytokine,extracellular vesicle,regeneration”。文献检索的时间范围为2000年1月至2021年12月,最终筛选出64篇文献进行分析。结果与结论:①脊髓损伤后,在细胞微环境的细胞组分中,占比最高的胶质细胞间的相互作用,以及与神经元的相互调控作用最为关键。②在脊髓损伤后的细胞外组分中,利用生物相容性良好的水凝胶模仿天然细胞外基质,可有效模拟和重建损伤区域内的细胞微环境,促进轴突伸长。③在脊髓损伤后的细胞外调节因子中,促炎因子如肿瘤坏死因子α和白细胞介素1β等加剧了细胞微环境的炎症反应,应用受体抑制剂或阻断相关通路抑制上述促炎因子的表达是一种有效的治疗方法,同时在脊髓微环境中增加白细胞介素10等抗炎因子的表达,抑制损伤区域炎症发展的研究也陆续出现。④最近被重视起来的细胞外囊泡作为传递信息的载体在细胞微环境中也发挥了重要作用。⑤文章揭示了脊髓损伤后细胞微环境中的包括细胞组分和细胞外组分之间的多组相互调控关系,证实了细胞微环境中各组分之间所发挥的神经修复作用并不是孤立的。

BACKGROUND:Previous studies have shown that a single change in the expression of a gene or the state of a cell in the area of spinal cord injury has no significant effect on functional recovery after spinal cord injury.An increasing number of evidence shows that the regulation of cellular microenvironment after spinal cord injury is a key factor hindering the recovery of neurological function.OBJECTIVE:To review the biological characteristics of cellular microenvironment before and after spinal cord injury,including the effect and mechanism of mutual regulation among different kinds of cells and extracellular components on nerve repair after spinal cord injury.METHODS:The first author retrieved the databases including PubMed and Web of Science for articles published from January 2000 to December 2021 using the key words of“spinal cord injury,glial cell,neuron,immune cell,neural stem cell,extracellular matrix,cytokine,extracellular vesicle,regeneration”.Finally,64 articles were selected for analysis.RESULTS AND CONCLUSION:(1)After spinal cord injury,among the cellular components of the cellular microenvironment,the interaction among glial cells,which account for the highest proportion,and the interaction with neurons are particularly critical.(2)Among the extracellular components after spinal cord injury,the hydrogels with good biocompatibility used to imitate natural extracellular matrix can effectively simulate and reconstruct the cellular microenvironment in the injured area and promote axonal elongation.(3)Among the extracellular regulatory factors after spinal cord injury,pro-inflammatory factors such as tumor necrosis factor-αand interleukin-1βaggravate the inflammatory storm of cellular microenvironment.Using receptor inhibitors or blocking related pathways to down-regulate the expression of adverse extracellular regulatory factors is an effective therapeutic method in the cellular microenvironment.At the same time,there are also studies on increasing the expression of anti-inflammatory factors such as interleukin-10 in the microenvironment of the spinal cord and on inhibiting the development of inflammation in the injured area.(4)Recently,extracellular vesicles have also played an important role in the cellular microenvironment as carriers of information.(5)This article reveals multiple sets of mutual regulatory relationships between cellular components and extracellular components in the cellular microenvironment after spinal cord injury,emphasizing that the neuroreparative effects of various components in the cellular microenvironment are not isolated.