Enhanced Migration of Neural Stem Cells by Microglia Grown on a Three-Dimensional Graphene Scaffold

Enhanced Migration of Neural Stem Cells by Microglia Grown on a Three-Dimensional Graphene Scaffold
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DOI:
10.1021/acsami.6b06780
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发表时间:
2016-09-28
影响因子:
9.5
通讯作者:
Cheng, Guosheng
Cheng, Guosheng
中科院分区:
材料科学2区
文献类型:
--
作者:
Jiang, Ziyun;Song, Qin;Cheng, Guosheng

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神经组织工程化的关键挑战之一是开发一种生物相容性支架材料来指导神经干细胞(NSC)的行为。支架的一大优点是在再生和修复过程中诱导NSC向病理部位迁移。特别是主要由中枢神经系统小胶质细胞介导的病理区炎症反应,通过NSC迁移影响NSCs的修复能力。近年来,石墨烯被用作神经界面和支架材料,但很少有研究涉及小胶质细胞之间的关系。和石墨烯培养系统中的NSCs。在这项研究中,我们使用免疫荧光、Western blotting、酶联免疫吸附试验和扫描电镜相结合的方法来研究由生长在二维石墨烯(2D-G)薄膜或三维石墨烯(3D-G)泡沫上的小胶质细胞产生的条件培养基(CM)如何影响NSC迁移。结果表明,3D-G培养的小胶质细胞产生的CM可通过激活基质细胞衍生因子1 α (SDF-1 α)/CXC趋化因子受体4 (CXCR4)信号通路和增强细胞对底物的粘附,促进神经球形成,促进NSC从神经球迁移,增加单细胞极化。相比之下,2D-G CM未能达到这些结果。我们的研究表明3D-G作为神经支架在组织工程和再生医学中基于nsc治疗的巨大潜力。
One of the key challenges in engineering neural tissues for cell-based therapies is to develop a biocompatible scaffold material to direct neural stem cell (NSC) behaviors. One great advantage for a scaffold would be to induce NSC migration toward pathological sites during regeneration and repair. In particular, the inflammatory responses in the pathological zone, which are mainly mediated by microglia in the central nervous system, affect the repair capacity of NSCs through NSC migration. Recently, graphene was used as a neural interface and scaffold material, but few studies have addressed the relationship between microglia. and NSCs in a graphene culture system. In this study, we used a combination of immunofluorescence, Western blotting, :enzyme-linked immunosorbent assays, and scanning electron microscopy to investigate how conditioned medium (CM) produced from microglia grown on two-dimensional graphene (2D-G) films or three-dimensional graphene (3D-G) foams govern NSC migration. The results revealed that the CM produced by microglia grown in 3D-G cultures could promote neurosphere formation, facilitate NSC migration from the neurospheres, and increase single cell polarization by activating the stromal cell-derived factor 1 alpha (SDF-1 alpha)/CXC chemokine-receptor 4 (CXCR4) signaling pathway and enhancing cell adhesion on the substrate. By contrast, the 2D-G CM failed to achieve these results. Our study suggests the great potential of 3D-G as a neural scaffold for NSC-based therapy in tissue engineering and regenerative medicine.