Department of Neurology, First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, China.
J Neurol Sci. 2012 May 15;316(1-2):141-9. doi: 10.1016/j.jns.2012.01.001. Epub 2012 Jan 26.
Stromal cell-derived factor-1 (SDF-1) and its cognate receptor, chemokine (C-X-C motif) receptor 4 (CXCR4), are involved in the migration of stem cells.
To test the hypothesis that mesenchymal stem cells (MSCs) with genetically modified CXCR4 can promote their own recruitment around the ischemic core.
Lentiviral vectors were used to overexpress the CXCR4-eGFP fusion protein (CXCR4/eGFP) or eGFP only (eGFP) or to introduce siRNA targeting endogenous CXCR4 (siRNA/eGFP) in rat mesenchymal stem cells (rMSCs). Rats were injected with either the transduced rMSCs or PBS as a control via the femoral vein following a left middle cerebral artery occlusion (MCAO).
One week after MCAO, immunofluorescence staining revealed a significant increase in the number of eGFP-positive cells surrounding the infarct areas in the CXCR4-rMSC-treated group compared to the rMSC-treated control group. Conversely, there was a significant reduction in the number of eGFP-positive cells in the siRNA-rMSC-treated group. Moreover, there was an increase in the capillary vascular volume of the peri-infarct area, a reduction in the volume of the cerebral infarction and improved neurological function in the CXCR4-rMSC-treated group compared to those in the rMSC-, siRNA-rMSC- or PBS-treated groups.
CXCR4 overexpression in the rMSCs promoted their mobilization and enhanced neuroprotection in a rat cerebral ischemia model. This strategy may be a useful therapeutic approach for treating ischemic stroke.
基质细胞衍生因子-1（SDF-1）及其同源受体趋化因子（C-X-C 基序）受体 4（CXCR4）参与干细胞的迁移。
验证这样一个假设，即经过基因修饰表达 CXCR4 的间充质干细胞（MSCs）可以促进其在缺血核心周围的募集。
慢病毒载体用于过表达 CXCR4-eGFP 融合蛋白（CXCR4/eGFP）或仅表达 eGFP（eGFP），或引入靶向内源性 CXCR4 的 siRNA（siRNA/eGFP），用于大鼠间充质干细胞（rMSCs）。大鼠通过股静脉注射转导的 rMSCs 或 PBS（作为对照），在左大脑中动脉闭塞（MCAO）后进行。
MCAO 后 1 周，免疫荧光染色显示，与 rMSC 治疗对照组相比，CXCR4-rMSC 治疗组梗死区周围的 eGFP 阳性细胞数量显著增加。相反，在 siRNA-rMSC 治疗组中，eGFP 阳性细胞的数量显著减少。此外，CXCR4-rMSC 治疗组的梗死周围区毛细血管血管容积增加，脑梗死体积减少，神经功能改善，与 rMSC、siRNA-rMSC 或 PBS 治疗组相比。
rMSCs 中 CXCR4 的过表达促进了其动员，并增强了大鼠脑缺血模型中的神经保护作用。这种策略可能是治疗缺血性中风的一种有用的治疗方法。
