经鼻给脐血间充质干细胞条件培养基治疗脑缺血再灌注损伤

Intranasal administration of the conditioned medium of human umbilical cord-derived mesenchymal stem cells for treatment of cerebral ischemia-reperfusion injury

背景:人脐血间充质干细胞分泌细胞因子和神经营养因子对大鼠脑缺血再灌注损伤具有神经保护作用,但经鼻给予人脐血间充质干细胞条件培养基治疗脑卒中的研究报道较少。目的:观察经鼻给人脐血间充质干细胞条件培养基对脑缺血再灌注损伤大鼠神经功能恢复的影响。方法:制备成年大鼠右侧大脑中动脉脑缺血再灌注模型,体外分离培养健康人脐血间充质干细胞,制备含有人脐血间充质干细胞分泌物质的条件培养基。造模后大鼠随机分为3组:对照组,单纯培养基对照组和条件培养基治疗组,各组每天经鼻给生理盐水、培养基DMEM/F12、条件培养基(10 mL/kg)治疗,术后1,7,14 d分别进行神经功能缺损评分、足错步试验。结果与结论:术后第1天,各组神经功能缺损评分、足错步次数比较差异无显著性意义(P>0.05)。术后第7,14天,对照组与单纯培养基组神经功能缺损评分、足错步次数比较,差异无显著性意义(P>0.05)。条件培养基治疗组神经功能缺损评分、足错步次数均明显少于对照组和单纯培养基组,差异有显著性意义(P<0.05)。说明经鼻给人脐血间充质干细胞条件培养基可明显促进缺血再灌注后大鼠神经功能的恢复。

BACKGROUND： Cytokines and neurotrophic factors secreted from human umbilical cord blood-derived mesenchymal stem cells secrete have neuroprotective effects on cerebral ischemia-reperfusion injury, but there are few reports about intranasal administration of human umbilical cord blood-derived mesenchymal stem cell conditioned medium in the treatment of stroke. OBJECTIVE： To investigate the protective effects of intranasal administration of human umbilical cord-derived mesenchymal stem cells-conditioned medium on neurologic function of rats with cerebral ischemia-reperfusion injury. METHODS： Adult rats were subjected to 2 hours of right middle cerebral artery occlusion and the human umbilical cord-derived mesenchymal stem cells were isolated from the postpartum human cord. We made the conditioned medium of human umbilical cord-derived mesenchymal stem cells. Ischemic rats were randomized and assigned to three groups and were treated by intranasal routine starting 24 hours after middle cerebral arteryocclusion with： （1） saline for control group; （2） Dulbecco＇s modified Eagle＇s medium/Ham＇s nutrient mixture F-12 medium for medium control group; （3） conditioned medium treatment group （10mL/kg） daily for 14 days. Behavioral tests （foot fault test, and modified Neurological Severity Score） were performed before and at 1, 7, 14 days after middle cerebral artery occlusion. RESULTS AND CONCLUSION： There was no difference in the behavioral tests among the three groups at postoperatively 1 day （P 〉 0.05）. Compared to the control and medium control group rats, respectively, rats in the conditioned medium group significantly improved functional outcome after stroke in days 7 and 14 （P 〈 0.05）. There was also no significant difference in functional tests between the control group and medium control group in days 7 and 14 （P 〉 0.05）. These results suggest that human umbilical cord-derived mesenchymal stem cells-conditioned medium via intranasal administration can significantly improve neurologic functional outcome after cerebrar fschemia-reperfusion fnj＇ury.