Quantification of Oligodendrocyte Progenitor Cells in Human and Cat Optic Nerve:Implications for Endogenous Repair in Multiple Sclerosis

摘要

促进来源于少突胶质祖细胞(OP)的少突胶质细胞髓鞘再生,提高内源性修复是改善多发性硬化运动障碍的重要方法之一,其重要前提是明确人类中枢神经系统中有丰富的可分化为少突胶质细胞的OP细胞,而这需要有对中枢神经系统中的OP细胞进行鉴定的可靠方法.本研究采用多种方法对猫和人的视神经进行染色,根据相关结果获取可用于研究人尸体解剖标本OP细胞表达的抗原表型.OP细胞又被称为NG2细胞,广泛表达NG2蛋白,属于一个独立的胶质细胞亚型,由于其表达OP细胞系的转录因子Olig1和Olig2,因此与少突胶质细胞相关.虽然NG2细胞形态多样,与轴索及其它胶质细胞紧密联系,但所有NG2细胞都可以作为OP细胞进行分化,补充局部丢失的少突胶质细胞.研究发现,在人和猫的视神经及猫脊髓的白质和灰质中,NG2细胞在神经胶质细胞中所占比例不足5%,与少突胶质细胞的比例为1∶10.本研究结果显示,NG2细胞数量特别是相对少突胶质细胞不充足,这可对促进多发硬化内源性修复的方法提供线索.%In multiple sclerosis (MS),one strategy to reduce disability is enhancement of endogenous repair by remyelinating oligodendrocytes derived from oligodendrocyte progenitor cells (OP).An important prerequisite is determining the abundance of OP relative to oligodendrocytes in normal human central nervous system (CNS),which,in turn,requires reliable OP identification.To achieve this,cat and human optic nerves (ON) were subjected to varied preparation protocols,and the resultant neuroglial staining profiles correlated to generate an antigenic phenotype for OP applicable to human autopsy specimens.OP,interchangeably called NG2cells due to universal NG2 expression,were shown to comprise a separate class of neuroglial cells,related to oligodendrocytes by expression of the oligodendrocyte lineage transcription factors,Olig1 and Olig2.Despite their morphological complexity,including contact with axons and other neuroglia,NG2cells all appear capable of responding as OP to counter local oligodendrocyte loss.However,quantification revealed that NG2cells comprised less than 5% of the neuroglia and had a ratio to oligodendrocytes of about 1∶10,not only in human and cat ON but also in white and gray-matter regions of cat spinal cord.The finding that NG2cells are not abundant,particularly relative to oligodendrocytes,may have implications for efforts to enhance endogenous repair in MS.(c) 2010 Wiley-Liss,Inc.