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肿瘤坏死因子α、粒细胞集落刺激因子对经冠状动脉灌注骨髓间充质干细胞移植率的影响

The Effect of TNF-α and G-CSF on the Intracoronary Trans-plantation Rate of Rabbit Mesenchymal Stem Cells In Vivo
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摘要 研究肿瘤坏死因子α(Tumor necrosis factor-alpha,TNF-α)、粒细胞集落刺激因子(Granulocyte-colony stimulationfactor,G-CSF)对经冠状动脉灌注骨髓间充质干细胞(Mesenchymal stem cells,MSCs)移植率的影响。选用2~3月龄健康日本大耳白兔,耳缘静脉注射阿霉素制作心肌损伤模型后随机分为3组:(1)空白对照组;(2)TNF-α组;(3)G-CSF组。每组7只。空白对照组移植前种子细胞及动物均不用细胞因子干预;TNF-α组移植前1d经耳缘静脉注入TNF-α(5μg/kg),种子细胞在移植12h前加入TNF-α(10ng/ml)进行预处理;G-CSF组移植前3d开始肌肉注射G-CSF(10μg/kg),每d一次;种子细胞在移植前12h加入G-CSF(10ng/ml)进行预处理。密度梯度离心法获取MSCs,体外扩增后4,6-二脒-2-苯基吲哚(DAPI)标记,主动脉根部球囊封堵方法移植细胞;4周后制作心肌组织切片计数移植细胞并进行统计学分析。TNF-α组及G-CSF组兔心肌内移植的细胞数明显多于空白对照组,差异有统计学意义(P<0.001)。提示体外培养的MSCs和心肌损伤模型经细胞因子TNF-α、G-CSF干预后,能提高经冠状动脉移植骨髓间充质干细胞的移植率。其可能机制与细胞因子TNF-α、G-CSF能提高MSCs与心脏微血管内皮细胞(Cardiac microvasculature endothelium CMVE)的黏附能力有关。 To investigate effects of tumor necrosis factor-alpha(TNF-α) and granulocyte-colony stimulation factor(G-CSF) on the transplantation rate of rabbit mesenchymal stem eells(MSCs) through intracoronary injection. Japanese white ears rabbits(2-3 months old) were used as myocardial injury models by intravenously injecting adriamycin, then they were divided into three gro ups randomly: (1) Blank group ; (2) TNF-α group ; (3) G-CSF group. There were 7 rabbits each group. Before transplantation, MSCs and rabbit models were neither intervened by cytokine in blank group;in TNF-αgroup, rabbits were injected TNF-α(5μg/kg) through ear-edge vein one day before transplantation, MSCs were pretreated by TNF-α(10ng/ml)12 hours before transplantation. In G-CSF group, rabbits were injected G-CSF(10μg/kg) intramuscular each day 3 days before transplantation. MSCs were pretreated by G-CSF(10 ng/ ml) 12 hours before transplantation. Separated by density gradient centrifugation and labeled by 4,6-biamidine-2-phenyliodole(DAPI) after cells expanded in vitro, MSCs were then transplanted through the root of aorta when the ascending aorta occluded above the sinus aortae. Myocardial pathological sections were made after 4 weeks and count transplanted cells under laser scanning confocal microscope and statiscally analyze. The amount of cells transplanted in rabbit myocardial were much more in TNF-α group G-CSF group than in blank group,there was statistically significant difference (P〈0. 001). It sugested that TNF-α and G-CSF intervened the cultured MSCs, and animal model of myocardial injury could elevate the transplantation rate of intracoronary injection rabbit mesenchymal stem cells. The mechanism may have relation to that cytokine can enhance the attachment of MSCs to cardiac microvascular endothelium(CMVE).
出处 《生物医学工程学杂志》 CAS CSCD 北大核心 2009年第5期1077-1081,共5页 Journal of Biomedical Engineering
基金 四川省教育厅重点资助项目(2004c001)
关键词 肿瘤坏死因子Α 粒细胞刺激因子 骨髓间充质干细胞 移植率 Tumor necrosis factor-alpha(TNF-α) Granulocyte-colony stimulation factor(G-CSF) Mesenchymal stem eell(MSCs) Transplantation rate Rabbit
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