移植嗅鞘细胞治疗脱髓鞘疾病如多发性硬化(MS)显示潜在的临床应用前景，其迁移对促神经再生和再髓鞘化起关键作用。Sema3A是一神经导向因子，高表达于多发性硬化病人中，但是否对移植的嗅鞘细胞迁移、促神经再生和再髓鞘起作用不清楚。前期发现:①Sema3A受体高表达于嗅鞘细胞；②Sema3A引起嗅鞘细胞前导突起塌缩，抑制迁移。由此设想：在移植治疗MS中，Sema3A抑制嗅鞘细胞迁移，抑制其促神经再生和再髓鞘能力；移植嗅鞘细胞联合注射Sema3A抑制剂，对于治疗MS具有协同效应。拟将采用动物模型、敲除小鼠等技术检测EAE模型中Sema3A时空表达分布；其次，基于Sema3A EAE模型阐明Sema3A对对移植的嗅鞘细胞迁移、促神经再生影响和机制；最后，检测移植嗅鞘细胞联合Sema3A抑制剂治疗EAE是否具有协同作用。这些研究为嗅鞘细胞移植治疗MS研究提供新思路和新策略。

Olfactory ensheathing cells（OECs）transplantation has emerged as a promising experimental therapy for treating demyelinated diseases such as multiple sclerosis(MS). Druing transplantation, the migration of OECs is critical for promoting the neural regeneration and remyelination. Semaphorin3A(Sema3A) is a typical repellant cue for axon guidance, and highly expressed in the brain of multiple sclerosis patients. However, whether Sema3A regulates the migration, neural regeneration and remyelination of OECs remains unclear. Our preliminary data has shown that: ①Sema3A receptors were highly expressed in OECs; ②Sema3A induced the collapse of leading front of OECs, and inhibited OEC migration. Based on these preliminary data, we propose our hypothesis: during transplantation for treating MS, Sema3A inhibits the neural regeneration and remyelination of OEC through inhibiting OEC migration; and OEC transplantation combiding with Sema3A antagonist are more effective to treat MS. To test this hypothesis, we will further examine the spatial and temprol expression pattern of Sema3A in EAE model; and then examine the roles and mechanisms of Sema3A in OEC migration and promotion of neural regernation during OEC transplantation using cellular and molecular technologies and Sema3A knockout mice EAE model . Finally, we will exmamine whether OEC transplantation combining with Sema3A antagonist are more effective to treat EAE (experimental autoimmune encephalomyelitis, EAE) based on EAE model (MS animal model) and Sema3A knockout mice. These studies will provide novel insights and strategies of OEC transplantation for treating demyelinated diseases.