Abstract：
The therapeutic application of neural stem cells (NSCs) in the central nerve system (CNS) injury is a promising strategy for combating irreversible neuronal loss. However, a variety of obvious inflammatory responses following nerve injury rapidly create an unfavorable microenvironment for survival and neuronal differentiation of NSCs in lesion area, limiting the efficacy of NSC-based therapy for CNS injury. It remained unknown how to effectively increase the neuronal differentiation efficiency of NSCs through transplantation. Here, we demonstrated that curcumin (CCM)-activated olfactory ensheathing cells (aOECs) effectively promoted neuronal differentiation of NSCs in the activated microglial inflammatory condition, and co-transplantation of aOECs and NSCs improved neurological recovery of rats after spinal cord injury (SCI), as evidenced by higher expression levels of neuronal markers and lower expression levels of glial markers in the differentiated cells, greater number of Tuj-1-positive cells as well as higher Basso, Beattie, and Bresnahan (BBB) locomotor scale, compared to the corresponding controls. Pathologically, hematoxylin and eosin (HE) staining and immunostaining also showed that aOECs remarkably enhanced the in vivo neuronal differentiation of NSCs and migration, and nerve repair. Further analysis revealed that the underlying mechanisms of aOECs potentiating the neuronal conversion of NSCs under inflammatory environment were tightly associated with up-regulation of anti-inflammatory cytokines and neurotrophic factors in OECs, and importantly, the activation of Wnt3/β-catenin pathway was likely involved in the mechanisms underlying the observed cellular events. Therefore, this study provides a promising strategy for SCI repair by co-transplantation of aOECs and NSCs.
摘要：
神经干细胞（NSC）在中枢神经系统（CNS）损伤中的治疗应用是对抗不可逆神经元损失的有希望的策略。然而,神经损伤后各种明显的炎性反应迅速为损伤区神经干细胞的存活和神经元分化创造了不利的微环境,限制基于NSC的治疗对中枢神经系统损伤的疗效。如何通过移植有效提高神经干细胞的神经分化效率，目前尚不清楚。这里,我们证明了姜黄素（CCM）激活的嗅鞘细胞（aOECs）在激活的小胶质细胞炎症状态下有效促进神经干细胞的神经元分化，同时联合移植神经干细胞和aOECs可改善大鼠脊髓损伤后的神经功能恢复,分化细胞中神经元标志物的表达水平较高，神经胶质标志物的表达水平较低，更多的Tuj-1阳性细胞以及更高的Basso，Beattie,和布雷斯纳汉（BBB）运动量表，与相应的对照相比。病理上,苏木素和伊红（HE）染色和免疫染色也显示aOECs显著增强了神经干细胞的体内神经元分化和迁移，和神经修复。进一步的分析表明，在炎症环境下，aOECs促进神经干细胞神经元转化的潜在机制与OECs中抗炎细胞因子和神经营养因子的上调密切相关。而且重要的是,Wnt3/β-catenin通路的激活可能与观察到的细胞事件的潜在机制有关.因此,本研究为通过aOECs和NSC的共移植修复SCI提供了一种有希望的策略。
