Interactions of chemokines and chemokine receptors mediate the migration of mesenchymal stem cells to the impaired site in the brain after hypoglossal nerve injury
Interactions of chemokines and chemokine receptors mediate the migration of mesenchymal stem cells to the impaired site in the brain after hypoglossal nerve injury
复制标题
DOI：
10.1634/stemcells.22-3-415
复制
发表时间：
2004-01-01
期刊：
影响因子：
5.2
通讯作者：
Tay, SSW
中科院分区：
文献类型：
--
作者：
Ji, JF;He, BP;Tay, SSW
间充质干细胞（MSC），离体培养，最近被证明能够迁移到脑损伤部位时，移植全身或局部，这表明MSC具有迁移能力。然而，这些细胞迁移的机制仍不清楚。在这项研究中，我们研究了一些趋化因子及其受体在大鼠骨髓间充质干细胞（rMSCs）在大鼠左舌下神经损伤模型中的作用。移植到侧脑室的大鼠脑的rMSCs迁移到撕脱的舌下神经核，在那里的趋化因子，基质细胞衍生因子1（SDF-1），和fractalkine的表达被观察到增加。术后1周和2周，这种增加暂时抑制了rMSCs向撕脱核的迁移。已经发现，rMSC表达CXCR 4和CX（3）CR 1，它们分别是SDF-1和fractalkine的受体，以及其他趋化因子受体CCR 2和CCR 5。此外，体外分析显示，重组人SDF-1 α（rhSDF-1 α）和重组大鼠fractalkine（rrfractalkine）诱导rMSCs迁移的G蛋白依赖性的方式。脑内注射rhSDF-1 α也被证明可以刺激移植的rMSCs归巢到脑内注射部位。这些数据表明，fractalkineCX（3）CR 1和SDF-1-CXCR 4的相互作用可以部分介导移植rMSCs的运输。这项研究为理解移植rMSCs的运输机制提供了重要的见解，也显着扩大了MSCs在脑损伤和疾病细胞治疗中的潜在作用。
Mesenchymal stem cells (MSCs), cultured ex vivo, recently were shown to be able to migrate into sites of brain injuries when transplanted systemically or locally, suggesting that MSCs possess migratory capacity. However, the mechanisms underlying the migration of these cells remain unclear. In this study, we examined the role of some chemokines and their receptors in the trafficking of rat MSCs (rMSCs) in a rat model of left hypoglossal nerve injury. rMSCs transplanted into the lateral ventricles of the rat brain migrated to the avulsed hypoglossal nucleus, where the expression of chemokines, stromal-cell-derived factor 1 (SDF-1), and fractalkine was observed to be increased. This increase temporally paralleled the migration of rMSCs into the avulsed nucleus at 1 and 2 weeks after operation. It has been found that rMSCs express CXCR4 and CX(3)CR1, the respective receptors for SDF-1 and fractalkine, and other chemokine receptors, CCR2 and CCR5. Furthermore, in vitro analysis revealed that recombinant human SDF-1 alpha (rhSDF-1alpha) and recombinant rat fractalkine (rrfractalkine) induced the migration of rMSCs in a G-protein-dependent manner. Intracerebral injection of rhSDF-1alpha has also been shown to stimulate the homing of transplanted rMSCs to the site of injection in the brain. These data suggest that the interactions of fractalkineCX(3)CR1 and SDF-1-CXCR4 could partially mediate the trafficking of transplanted rMSCs. This study provides an important insight into the understanding of the mechanisms governing the trafficking of transplanted rMSCs and also significantly expands the potential role of MSCs in cell therapy for brain injuries and diseases.