Dombrowski Mary A, Sasaki Masanori, Lankford Karen L, Kocsis Jeffery D, Radtke Christine
Department of Neurology and Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, CT 06510, USA.
Brain Res. 2006 Dec 13;1125(1):1-8. doi: 10.1016/j.brainres.2006.09.089. Epub 2006 Nov 16.
Transplantation of olfactory ensheathing cells (OECs) into injured spinal cord results in improved functional outcome. Mechanisms suggested to account for this functional improvement include axonal regeneration, remyelination and neuroprotection. OECs transplanted into transected peripheral nerve have been shown to modify peripheral axonal regeneration and functional outcome. However, little is known of the detailed integration of OECs at the transplantation site in peripheral nerve. To address this issue, cell populations enriched in OECs were isolated from the olfactory bulbs of adult green fluorescent protein (GFP)-expressing transgenic rats and transplanted into a sciatic nerve crush lesion which transects all axons. Five weeks to 6 months after transplantation, the nerves were studied histologically. GFP-expressing OECs survived in the lesion and distributed longitudinally across the lesion zone. The internodal regions of individual teased fibers distal to the transection site were characterized by GFP expression in the cytoplasmic and nuclear compartments of cells surrounding the axons. Immunoelectron microscopy for GFP indicated that the transplanted OECs formed peripheral type myelin. Immunostaining for sodium channel and Caspr revealed a high density of Na(v)1.6 at the newly formed nodes of Ranvier which were flanked by paranodal Caspr staining. These results indicate that transplanted OECs extensively integrate into transected peripheral nerve and form myelin on regenerated peripheral nerve fibers, and that nodes of Ranvier of these axons display proper sodium channel organization.
将嗅鞘细胞（OECs）移植到脊髓损伤部位可改善功能预后。据推测，导致这种功能改善的机制包括轴突再生、髓鞘再生和神经保护。已证实，移植到横断外周神经中的OECs可改变外周轴突再生和功能预后。然而，关于OECs在周围神经移植部位的详细整合情况知之甚少。为解决这一问题，从成年绿色荧光蛋白（GFP）表达转基因大鼠的嗅球中分离出富含OECs的细胞群体，并将其移植到切断所有轴突的坐骨神经挤压损伤处。移植后5周或6个月，对神经进行组织学研究。表达GFP的OECs在损伤部位存活，并沿损伤区域纵向分布。横断部位远端单个分离纤维的结间区域，其轴突周围细胞的细胞质和细胞核内均有GFP表达。GFP免疫电子显微镜检查表明，移植的OECs形成了外周型髓磷脂。钠通道和Caspr免疫染色显示，在新形成的郎飞结处Na（v）1.6密度很高，其两侧为结旁Caspr染色。这些结果表明，移植的OECs广泛整合到横断的周围神经中，并在再生的周围神经纤维上形成髓磷脂，且这些轴突的郎飞结具有正常的钠通道组织。
