Haberberger Rainer Viktor, Barry Christine, Matusica Dusan
Anatomy & Histology, College of Medicine and Public Health, Flinders Health & Medical Research Institute, Flinders University, Adelaide, SA, Australia.
Front Cell Neurosci. 2020 Jun 19;14:184. doi: 10.3389/fncel.2020.00184. eCollection 2020.
Pain is one of the most significant causes of suffering and disability world-wide, and arguably the most burdensome global health challenge. The growing number of patients suffering from chronic pain conditions such as fibromyalgia, complex regional pain syndrome, migraine and irritable bowel syndrome, not only reflect the complexity and heterogeneity of pain types, but also our lack of understanding of the underlying mechanisms. Sensory neurons within the dorsal root ganglia (DRG) have emerged as viable targets for effective chronic pain therapy. However, DRG's contain different classes of primary sensory neurons including pain-associated nociceptive neurons, non-nociceptive temperature sensing, mechanosensory and chemoreceptive neurons, as well as multiple types of immune and endothelial cells. This cell-population heterogeneity makes investigations of individual subgroups of DRG neurons, such as nociceptors, difficult. In attempts to overcome some of these difficulties, a limited number of immortalized DRG-derived cell lines have been generated over the past few decades. experiments using DRG-derived cell lines have been useful in understanding sensory neuron function. In addition to retaining phenotypic similarities to primary cultured DRG neurons, these cells offer greater suitability for high throughput assays due to ease of culture, maintenance, growth efficiency and cost-effectiveness. For accurate interpretation and translation of results it is critical, however, that phenotypic similarities and differences of DRG-derived cells lines are methodically compared to native neurons. Published reports to date show notable variability in how these DRG-derived cells are maintained and differentiated. Understanding the cellular and molecular differences stemming from different culture methods, is essential to validate past and future experiments, and enable these cells to be used to their full potential. This review describes currently available DRG-derived cell lines, their known sensory and nociceptor specific molecular profiles, and summarize their morphological features related to differentiation and neurite outgrowth.
疼痛是全球范围内导致痛苦和残疾的最重要原因之一,可以说是最具负担的全球健康挑战。患有纤维肌痛、复杂性区域疼痛综合征、偏头痛和肠易激综合征等慢性疼痛疾病的患者数量不断增加,这不仅反映了疼痛类型的复杂性和异质性,也反映出我们对其潜在机制缺乏了解。背根神经节(DRG)内的感觉神经元已成为有效的慢性疼痛治疗的可行靶点。然而,DRG包含不同类型的初级感觉神经元,包括与疼痛相关的伤害性神经元、非伤害性温度传感神经元、机械感觉神经元和化学感受神经元,以及多种类型的免疫细胞和内皮细胞。这种细胞群体的异质性使得对DRG神经元的各个亚组(如伤害感受器)进行研究变得困难。为了克服其中一些困难,在过去几十年中已经产生了有限数量的永生化DRG衍生细胞系。使用DRG衍生细胞系进行的实验有助于理解感觉神经元的功能。除了与原代培养的DRG神经元保持表型相似性外,这些细胞由于易于培养、维持、生长效率高和成本效益好,更适合进行高通量检测。然而,为了准确解释和转化结果,至关重要的是将DRG衍生细胞系的表型异同与天然神经元进行系统比较。迄今为止发表的报告表明,这些DRG衍生细胞的维持和分化方式存在显著差异。了解不同培养方法导致的细胞和分子差异,对于验证过去和未来的实验以及充分发挥这些细胞的潜力至关重要。这篇综述描述了目前可用的DRG衍生细胞系、它们已知的感觉和伤害感受器特异性分子谱,并总结了它们与分化和神经突生长相关的形态学特征。