The influence of transplantation of human umbilical cord blood derived mesenchymal stem cells on cerebral angiogenesis and related secreted cytokines in rats after traumatic brain injury
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摘要: 目的:探讨人脐血间充质干细胞(MSCs)移植对大鼠创伤性脑损伤模型的脑保护作用机制。方法:将用Brdu标记的人脐血间充质干细胞MSCs经鼠尾静脉植入经改进Feeney自由落体方法制作的大鼠TBI模型。采用苏木精-伊红染色、免疫组织化学、原位杂交对TBI大鼠注射后各组不同时间点的脑组织光镜下形态学变化、移植细胞迁移、损伤周边区血管新生相关因子表达及血管新生情况进行观察和比较,并以NSS方法行神经损伤严重程度评分。结果:经Brdu标记的细胞在损伤周边区明显聚集,4周后仍可见,且未发生移植相关的死亡。组织学检测可见实验组损伤严重程度病理改变较对照组轻微;实验组大鼠脑损伤周边区微血管密度,碱性成纤维细胞生长因子(bFGF)、血管内皮细胞生长因子(VEGF)、VEGF mRNA阳性细胞的表达明显增加(P<0.05)。结论:未应用免疫抑制剂的情况下,经尾静脉注射MSCs可以迁移至免疫功能健全的大鼠脑创伤灶周边区,促进VEGF mRNA分泌、血管新生相关因子(VEGF、bFGF)分泌及血管新生,改善神经功能。Abstract: Objective:To study the effects of intravenous administration of human umbilical cord blood mesenchymal stem cells(HUCBMSCs)on TBI(traumatic brain injury)rats.Method:The rats treated by modified Feeney free-falling method were injected with 3×106 HUCBMSCs labelled by Brdu(5-bromo-2-deoxyuridine)via tail vein.HE staining,immunohistochemistry,in situ hybridization were used to compare the morphological changes, the expression of VEGF mRNA,bFGF and VEGF,as well as angiogenesis situation of brain tissue in TBI rats at different time points after injection(3,7,14,21,28 d).The rats were killed at corresponding time points before evaluating the neurological severity score points(NSS).Result:Cells labelled by Brdu in the treatment group obviously gathered in the injured area and stayed for at least four weeks.NSS score showed that neurological function of treatment group was significantly improved compared with control group.Under light microscopy,pathological changes of rats in treatment group were much slighter than those in control group.The expression of VEGF,bFGF,VEGF mRNA positive cells and the microvessell density(MVD)in the injured cortex was significantly higher in treatment group than that in control group at each time point after TBI(P<0.05).Conclusion:Without the administration of immunosuppressants,intravenous-injected HUCBMSCs can migrate to peripheral zone of traumatic brain injury area of heterogeneous rats,improve angiogenesis in TBI rats by upregulating the secretion of related cytokine(VEGF mRNA,VEGF and bFGF)and promote the functional recovery of neurons.
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