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  • 石凯燕,张春雪,王艺静,等.人源脐带间充质干细胞对脑缺血再灌注小鼠神经功能及神经炎症的影响[J].同济大学学报(医学版),2020,41(5):537-545.    [点击复制]
  • SHI Kai-yan,ZHANG Chun-xun,WANG Yi-jing,et al.Effects of human Wharton’s Jelly derived mesenchymal stem cells on neural function and neuroinammation in cerebral ischemic/reperfusion mice[J].同济大学学报(医学版),2020,41(5):537-545.   [点击复制]
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人源脐带间充质干细胞对脑缺血再灌注小鼠神经功能及神经炎症的影响
石凯燕,张春雪,王艺静,王臻,孙毅
0
(同济大学医学院,上海200092;同济大学医学院,上海200092;同济大学附属同济医院干细胞临床转化中心,上海200065)
摘要:
目的探究人源脐带间充质干细胞对脑缺血再灌注损伤小鼠神经功能及神经炎症的影响。方法将96只野生型C57BL/6小鼠随机分为假手术组、磷酸盐缓冲液(PBS)处理组、WJ-MSCs细胞移植组,每组32只。PBS处理组和细胞移植组小鼠通过线栓法构建大脑中动脉阻塞再灌注模型;术后24h,通过脑立体定位技术注射细胞悬液或PBS溶液。每组取6只小鼠,于细胞移植后对小鼠腹腔注射BrdU溶液,持续5d。于术前及术后1、6、12、24d对各组小鼠进行改良神经功能损伤评分;术后6d时,采用神经元标志物NeuN免疫荧光单标记染色技术检测缺血侧大脑梗死灶及梗死灶周围区皮质神经元的变性丢失情况;采用RT-qPCR技术检测各组小鼠缺血侧大脑半球炎症因子的表达量;采用小胶质细胞/巨噬细胞标志物Iba1及增殖标记物BrdU免疫荧光双标记染色技术检测小胶质细胞/巨噬细胞的活化和增殖情况。结果与PBS处理组相比,WJ-MSCs细胞移植组小鼠神经功能显著改善(P<0.01),且位于缺血侧大脑梗死灶及梗死灶周围区皮质的存活神经元数目显著增多(P<0.01)。与PBS处理组相比,WJ-MSCs细胞移植组小鼠缺血侧脑组织的抗炎因子表达量升高,促炎因子表达量下降,差异具有统计学意义(P<0.05)。与PBS处理组相比,WJ-MSCs细胞移植组小鼠缺血侧梗死灶和梗死灶周围区皮质小胶质细胞/巨噬细胞的活化显著抑制(P<0.05),且小胶质细胞/巨噬细胞的增殖明显降低(P<0.05)。结论人源脐带间充质干细胞可抑制神经炎症反应并改善脑缺血再灌注小鼠的神经功能。
关键词:  脑缺血  脐带间充质干细胞  神经元  神经炎症  小胶质细胞/巨噬细胞
DOI:10.16118/j.1008-0392.2020.05.001
投稿时间:2020-04-07
基金项目:国家重点基础研究发展计划(“九七三”计划)(2016YFA0100801)
Effects of human Wharton’s Jelly derived mesenchymal stem cells on neural function and neuroinammation in cerebral ischemic/reperfusion mice
SHI Kai-yan,ZHANG Chun-xun,WANG Yi-jing,WANG Zhen,SUN Yi
(Tongji University School of Medicine,Shanghai 200092, China;Tongji University School of Medicine,Shanghai 200092, China; Translational Stem Cell Reseach Center,Tongji Hospital,Tongji University School of Medicine, Shanghai 200065,China)
Abstract:
Objective To investigate the effects of human Wharton’s Jelly-derived mesenchymal stem cells(hMJ-MSCs) on neural function and neuroinflammation in cerebral ischemic/reperfusion mice. MethodsNinety-six wild-type C57BL/6 mice were randomly divided into sham-operated group, phosphate buffered saline(PBS) control group, and WJ-MSCs transplantation group with 32 mice in each group. Mouse ischemia/reperfusion model was induced by transient middle cerebral artery occlusion(MCAO) through insertion of an intraluminal suture. PBS or cells suspension were intracerebrally injected with stereotaxical positioning 24h after the surgery in three groups. After cell transplantation, six mice in each group were injected intraperitoneally with BrdU solution for 5 days. Modified neurological severity tests were performed before, and 1, 6, 12 and 24d after surgery. RT-qPCR was used to analyze the mRNA expression of inflammatory factors in ischemic hemisphere at 6d after surgery. NeuN+ neurons were detected and counted throughout the infarcts and marginal cortex of cerebral ischemia by immunofluorescence. Double immunofluorescence staining with Iba1 and BrdU antibodies combined with image analysis was used to detect activation and proliferation of microglia/macrophages. ResultsIn comparison with the PBS control group, the neural function in the WJ-MSCs transplantation group significantly recovered(P<0.01) and exhibited significantly higher numbers of surviving neurons in the infarcts and marginal cortex of cerebral ischemia(P<0.01). Compared with the control group, mice in the WJ-MSCs transplantation group showed significantly higher mRNA expression of anti-inflammatory factor and lower mRNA expression of pro-inflammatory in the ischemic brain(P<0.05). Compared with the PBS control group, WJ-MSCs significantly attenuated the activation and proliferation of microglia/macrophages in the infarcts and marginal cortex of cerebral ischemia(P<0.05). Conclusion WJ-MSCs can inhibit neuroinflammation and promote recovery of neural function in cerebral ischemic mice.
Key words:  brain ischemia  Wharton’s jelly cells  neuron  neuroinammation  microglia/macrophage

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