基质细胞衍生因子-1对间质干细胞迁移的影响

目的:观察基质细胞衍生因子-1(SDF-1)在体内外对大鼠骨髓间质干细胞(rMSCs)的趋化诱导作用,探讨SDF-1对rMSCs迁移影响的可能机制。方法:应用体外细胞迁移实验及大鼠脑梗死模型体内移植,观察SDF-1对rMSCs的迁移影响。流式细胞术与RT-PCR检测rMSCs的CXC趋化因子受体4(CXCchemokinereceptor4,CXCR4)表达。结果:在SDF-1存在时,rMSCs迁移活跃,应用抗体封闭CXCR4后,这种迁移显著减弱。体内移植的rMSCs主要聚集在脑梗死灶周围,但在封闭CXCR4后,这种聚集现象大大减弱。流式细胞术示仅小部分rMSCs表面表达CXCR4,但经TritonX-100处理后,表达CXCR4的rMSCs增加。结论:SDF-1可通过CXCR4对rMSCs起趋化作用,针对这种作用可望调控干细胞向靶组织的趋化聚集量,达到治疗目的。

Effect of Stromal Cell-derived Factor-1 on the Migration of Mesenchymal Stem Cells

Aim: To investigate the effect of stromal cell-derived factor-(1SDF-1)on the migration of mesenchymal stem cells(MSCs), and to explore the possible mechanism of this effect under the condition of brain ischemic injury. Methods: Effects of SDF-1 on the migration of cultural rat MSCs (rMSCs) and N9 microglial cells were observed by counting migrated cells and by calculating the migration indexes to show the difference of rMSCs migration under the conditions with or without the existence of SDF-1. CTO-labeled rMSCs were injected into the tail vein of rat with middle cerebral artery occlusion (MCAO). The migration and congregation of labeled cells in the injured region of brain sections were observed with fluorescence microscope. Anti-CXC chemokine receptor 4 (Anti-CXCR4) antibodies were used for blocking studies, and the expressions of CXC chemokine receptor 4(CXCR4)in rMSCs were observed with RT-PCR and flow cytometry respectively. Results: In vitro, the migration indexes of rMSCs and N9 microglial cells in the SDF-1 groups were significantly higher as compared with the medium control(sP<0.01). The CXCR4 antibody blocking significantly impaired the SDF-1 chemotaxis. In vivo, labeled rMSCs mainly migrated and congregatedaround the injured region in the rMSCs transplantation groups. The CXCR4 antibody also significantly impaired the migration and congregation of rMSCs. Conclusion: The results demonstrate that the chemotactic effect of SDF-1 on the MSCs is introduced by CXCR4. Although only small proportion of rMSCs expresses active extracellular CXCR4 receptor,there are higher level intracellular expression of CXCR4. SDF-1 secreted from injured brain tissue may be responsible for the chemotaxis and congregation of MSCs. This phenomenon will be significant in the therapeutical research of acute injury.