Department of Neuroregeneration, Netherlands Institute for Neuroscience, An Institute of the Royal Netherlands Academy of Arts and Sciences, Meibergdreef 47, 1105BA Amsterdam, The Netherlands.
Department of Neuroregeneration, Netherlands Institute for Neuroscience, An Institute of the Royal Netherlands Academy of Arts and Sciences, Meibergdreef 47, 1105BA Amsterdam, The Netherlands; Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, Boelelaan 1085, Amsterdam 1081HV, The Netherlands.
Exp Neurol. 2014 Nov;261:594-609. doi: 10.1016/j.expneurol.2014.05.007. Epub 2014 May 17.
Olfactory ensheathing glial cells (OECs) are a specialized type of glia that form a continuously aligned cellular pathway that actively supports unprecedented regeneration of primary olfactory axons from the periphery into the central nervous system. Implantation of OECs stimulates neural repair in experimental models of spinal cord, brain and peripheral nerve injury and delays disease progression in animal models for neurodegenerative diseases like amyotrophic lateral sclerosis. OECs implanted in the injured spinal cord display a plethora of pro-regenerative effects; they promote axonal regeneration, reorganize the glial scar, remyelinate axons, stimulate blood vessel formation, have phagocytic properties and modulate the immune response. Recently genome wide transcriptional profiling and proteomics analysis combined with classical or larger scale "medium-throughput" bioassays have provided novel insights into the molecular mechanism that endow OECs with their pro-regenerative properties. Here we review these studies and show that the gaps that existed in our understanding of the molecular basis of the reparative properties of OECs are narrowing. OECs express functionally connected sets of genes that can be linked to at least 10 distinct processes directly relevant to neural repair. The data indicate that OECs exhibit a range of synergistic cellular activities, including active and passive stimulation of axon regeneration (by secretion of growth factors, axon guidance molecules and basement membrane components) and critical aspects of tissue repair (by structural remodeling and support, modulation of the immune system, enhancement of neurotrophic and antigenic stimuli and by metabolizing toxic macromolecules). Future experimentation will have to further explore the newly acquired knowledge to enhance the therapeutic potential of OECs.
嗅鞘细胞（OECs）是一种特殊类型的神经胶质细胞，形成了一种连续排列的细胞通路，积极支持外周初级嗅神经轴突向中枢神经系统的前所未有的再生。OECs 的植入刺激了脊髓、大脑和周围神经损伤的实验模型中的神经修复，并延迟了肌萎缩侧索硬化症等神经退行性疾病的动物模型中的疾病进展。植入损伤脊髓中的 OECs 表现出多种促再生作用；它们促进轴突再生、重组神经胶质瘢痕、髓鞘再生轴突、刺激血管形成、具有吞噬特性并调节免疫反应。最近，全基因组转录组学和蛋白质组学分析结合经典或更大规模的“高通量”生物测定为赋予 OECs 促再生特性的分子机制提供了新的见解。在这里，我们回顾了这些研究，并表明我们对 OECs 修复特性的分子基础的理解中的差距正在缩小。OECs 表达功能上相互关联的基因集，这些基因集至少可以与 10 个直接与神经修复相关的不同过程相关联。这些数据表明，OECs 表现出一系列协同的细胞活性，包括对轴突再生的主动和被动刺激（通过分泌生长因子、轴突导向分子和基底膜成分）以及组织修复的关键方面（通过结构重塑和支持、免疫系统的调节、神经营养和抗原刺激的增强以及对有毒大分子的代谢）。未来的实验将不得不进一步探索新获得的知识，以增强 OECs 的治疗潜力。
