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脂肪来源的嗅鞘细胞通过上调生物活性因子和激活Wnt3/β-连环蛋白通路促进炎症微环境中神经干细胞的神经元分化。

The aOECs Facilitate the Neuronal Differentiation of Neural Stem Cells in the Inflammatory Microenvironment Through Up-Regulation of Bioactive Factors and Activation of Wnt3/β-Catenin Pathway.

作者信息

He Yuqing, Jiang Yizhen, Dong Lianwei, Jiang Chao, Zhang Lingling, Zhang Gaorong, Yang Hao, Liu Juan

机构信息

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.

出版信息

Mol Neurobiol. 2023 Feb;60(2):789-806. doi: 10.1007/s12035-022-03113-w. Epub 2022 Nov 12.


DOI:10.1007/s12035-022-03113-w
PMID:36371572
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(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。

相似文献

[1]
The aOECs Facilitate the Neuronal Differentiation of Neural Stem Cells in the Inflammatory Microenvironment Through Up-Regulation of Bioactive Factors and Activation of Wnt3/β-Catenin Pathway.

Mol Neurobiol. 2023-2

[2]
Curcumin-activated Olfactory Ensheathing Cells Improve Functional Recovery After Spinal Cord Injury by Modulating Microglia Polarization Through APOE/TREM2/NF-κB Signaling Pathway.

J Neuroimmune Pharmacol. 2023-9

[3]
Transplantation of activated olfactory ensheathing cells by curcumin strengthens regeneration and recovery of function after spinal cord injury in rats.

Cytotherapy. 2020-4-9

[4]
Mash-1 modified neural stem cells transplantation promotes neural stem cells differentiation into neurons to further improve locomotor functional recovery in spinal cord injury rats.

Gene. 2021-5-20

[5]
TRANSPLANTATION OF HYPERTHERMIC PRECONDITIONING OLFACTORY ENSHEATHING CELLS COMBINED WITH NEURAL STEM CELLS IN THE TREATMENT OF CENTRAL NERVE INJURY.

J Biol Regul Homeost Agents. 2015

[6]
A collagen microchannel scaffold carrying paclitaxel-liposomes induces neuronal differentiation of neural stem cells through Wnt/β-catenin signaling for spinal cord injury repair.

Biomaterials. 2018-8-22

[7]
Transplantation of olfactory ensheathing cells promotes the therapeutic effect of neural stem cells on spinal cord injury by inhibiting necrioptosis.

Aging (Albany NY). 2021-3-4

[8]
Release of O-GlcNAc transferase inhibitor promotes neuronal differentiation of neural stem cells in 3D bioprinted supramolecular hydrogel scaffold for spinal cord injury repair.

Acta Biomater. 2022-10-1

[9]
Metformin enhances endogenous neural stem cells proliferation, neuronal differentiation, and inhibits ferroptosis through activating AMPK pathway after spinal cord injury.

J Transl Med. 2024-8-5

[10]
Synergistic effect of neural stem cells and olfactory ensheathing cells on repair of adult rat spinal cord injury.

Cell Transplant. 2010-5-4

引用本文的文献

[1]
Effect of Dynamin-2 Gene Modified OECs on Functional and Molecular Neuroprotection After Spinal Cord Injury in Rats.

Neurochem Res. 2025-7-16

[2]
The significance of calcium ions in cerebral ischemia-reperfusion injury: mechanisms and intervention strategies.

Front Mol Biosci. 2025-5-12

[3]
Characteristics of quiescent adult neural stem cells induced by the bFGF/BMP4 combination or BMP4 alone .

Front Cell Neurosci. 2024-5-22

[4]
Interleukin-4 from curcumin-activated OECs emerges as a central modulator for increasing M2 polarization of microglia/macrophage in OEC anti-inflammatory activity for functional repair of spinal cord injury.

Cell Commun Signal. 2024-3-6

[5]
Neurotrophic and immunomodulatory effects of olfactory ensheathing cells as a strategy for neuroprotection and regeneration.

Front Immunol. 2022

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