Department of Neurology, University of Maryland School of Medicine, Baltimore, MD 21201, USA; VAMHCS, Baltimore, MD 21201, USA.
Neurochem Int. 2012 Nov;61(6):859-65. doi: 10.1016/j.neuint.2012.02.010. Epub 2012 Feb 15.
Transplantation of neural stem cells for replacing neurons after neurodegeneration requires that the transplanted stem cells accurately reestablish the lost neural circuits in order to restore function. Retinal ganglion cell axons project to visual centers of the brain forming circuits in precise topographic order. In chick, dorsal retinal neurons project to ventral optic tectum, ventral neurons to dorsal tectum, anterior neurons to posterior tectum and posterior neurons to anterior tectum; forming a continuous point-to-point map of retinal cell position in the tectal projection. We found that when stem cells derived from ventral retina were implanted in dorsal host retina, the stem cells that became ganglion cells projected to dorsal tectum, appropriate for their site of origin in retina but not appropriate for their site of implant in retina. This led us to ask if retinal progenitors exhibit topographic markers of cell position in retina. Indeed, retinal neural progenitors express topographic markers: dorsal stem cells expressed more Ephrin B2 than ventral stem cells and, conversely, ventral stem cells expressed more Pax-2 and Ventroptin than dorsal stem cells. The fact that neural progenitors express topographic markers has pertinent implications in using neural stem cells in cell replacement therapy for replacing projecting neurons that express topographic order, e.g., analogous neurons of the visual, auditory, somatosensory and motor systems.
神经干细胞移植替代神经退行性病变后的神经元，要求移植的干细胞能够准确重建丢失的神经网络，以恢复功能。视网膜神经节细胞轴突投射到大脑的视觉中枢，形成精确的拓扑排列的回路。在鸡中，背侧视网膜神经元投射到腹侧视顶盖，腹侧神经元投射到背侧顶盖，前侧神经元投射到后侧顶盖，后侧神经元投射到前侧顶盖；在视顶盖的投射中形成视网膜细胞位置的连续点对点图谱。我们发现，当源自腹侧视网膜的干细胞被植入背侧宿主视网膜时，变成神经节细胞的干细胞投射到背侧视顶盖，这与它们在视网膜中的起源部位相适应，但与它们在视网膜中的植入部位不适应。这使我们提出这样一个问题，即视网膜祖细胞是否表现出视网膜细胞位置的拓扑标记。事实上，视网膜神经祖细胞表达拓扑标记：背侧干细胞比腹侧干细胞表达更多的 Ephrin B2，相反，腹侧干细胞比背侧干细胞表达更多的 Pax-2 和 Ventroptin。神经祖细胞表达拓扑标记这一事实在使用神经干细胞进行细胞替代治疗时具有重要意义，例如，用于替代表达拓扑顺序的投射神经元，例如视觉、听觉、躯体感觉和运动系统的类似神经元。
