He Yuqing, Jiang Yizhen, Dong Lianwei, Jiang Chao, Zhang Lingling, Zhang Gaorong, Yang Hao, Liu Juan
School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, 750004, Ningxia, China.
Translational Medicine Center, Hong Hui Hospital, Xi'an Jiao Tong University, Xi'an 710054, China.
Mol Neurobiol. 2023 Feb;60(2):789-806. doi: 10.1007/s12035-022-03113-w. Epub 2022 Nov 12.
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.
神经干细胞(NSCs)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一种有前景的策略。然而,神经损伤后各种明显的炎症反应迅速为损伤区域NSCs的存活和神经元分化创造了不利的微环境,限制了基于NSCs的CNS损伤治疗的疗效。如何通过移植有效提高NSCs的神经元分化效率仍不清楚。在此,我们证明姜黄素(CCM)激活的嗅鞘细胞(aOECs)在激活的小胶质细胞炎症条件下有效促进了NSCs的神经元分化,并且aOECs与NSCs的共移植改善了脊髓损伤(SCI)大鼠的神经功能恢复,这表现为分化细胞中神经元标志物的表达水平较高,胶质细胞标志物的表达水平较低,Tuj-1阳性细胞数量更多,以及Basso、Beattie和Bresnahan(BBB)运动评分更高,与相应对照组相比。病理上,苏木精和伊红(HE)染色及免疫染色也显示aOECs显著增强了NSCs在体内的神经元分化、迁移及神经修复。进一步分析表明,aOECs在炎症环境下增强NSCs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,重要的是,Wnt3/β-连环蛋白通路的激活可能参与了所观察到的细胞事件的潜在机制。因此,本研究为aOECs与NSCs共移植修复SCI提供了一种有前景的策略。
Front Cell Neurosci. 2024-5-22