van den Pol Anthony N, Santarelli Justin G
Department of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
J Comp Neurol. 2003 Mar 31;458(2):175-94. doi: 10.1002/cne.10577.
Olfactory ensheathing cells (OECs) have considerable potential for facilitating axonal growth across regions of spinal cord and brain injury but in this context have been studied primarily in static images of fixed tissue from the olfactory system or after transplantation. In the present work, we studied the behavior of live OECs, and their interactions with neurons, Schwann cells, and astrocytes by using cells that express the reporter gene coding for green fluorescent protein (GFP); the work is based on combinations of fluorescence, phase contrast, digital time lapse imaging, and P75 immunocytochemical identification. Cultures, explants, and regions of olfactory system slices rich in OECs enhanced axonal growth of cerebellar granule cells or hippocampal neurons; axons grew parallel to the long axis of fusiform OECs. Neuron cell bodies and axons preferred OECs over artificial substrates. Axons and neuron cell bodies can take active or passive roles in extension and migration on underlying motile OECs and move from one OEC to another. Axon extension was facilitated to a similar degree by OECs and Schwann cells, whereas astrocytes were more likely to integrate with existing OECs than with Schwann cells. OECs showed a dramatic ability to rapidly change shape, size, and direction of migration and to undergo mitosis. Mitosis was characterized by a quick retraction of all processes, thereby forming a sphere that divided into spherical daughter cells within minutes. Progeny OECs might take on the parental or a non-parental morphotype, with both daughter cells showing robust expression of GFP. Together these OEC data demonstrated a substantial plasticity and capability for relatively rapid changes in structure and support the view that OECs have multiple attributes favorable for enhancing axonal extension and neuronal migration after central nervous system injury.
嗅鞘细胞(OECs)在促进轴突跨越脊髓和脑损伤区域生长方面具有巨大潜力,但在此背景下,主要是在来自嗅觉系统的固定组织的静态图像中或移植后对其进行研究。在本研究中,我们通过使用表达编码绿色荧光蛋白(GFP)的报告基因的细胞,研究了活的OECs的行为及其与神经元、雪旺细胞和星形胶质细胞的相互作用;这项工作基于荧光、相差、数字延时成像和P75免疫细胞化学鉴定的组合。富含OECs的嗅觉系统切片的培养物、外植体和区域增强了小脑颗粒细胞或海马神经元的轴突生长;轴突平行于梭形OECs的长轴生长。神经元细胞体和轴突在人工基质上更倾向于OECs。轴突和神经元细胞体在下方可移动的OECs上的延伸和迁移中可发挥主动或被动作用,并从一个OEC移动到另一个OEC。OECs和雪旺细胞促进轴突延伸的程度相似,而星形胶质细胞比雪旺细胞更有可能与现有的OECs整合。OECs表现出显著的能力,能够迅速改变形状、大小和迁移方向并进行有丝分裂。有丝分裂的特征是所有突起迅速回缩,从而形成一个球体,该球体在几分钟内分裂成球形子细胞。子代OECs可能呈现亲代或非亲代形态类型,两个子细胞均显示出GFP的强表达。这些OECs数据共同证明了其具有显著的可塑性以及结构相对快速变化的能力,并支持这样一种观点,即OECs具有多种有利于增强中枢神经系统损伤后轴突延伸和神经元迁移的特性。