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Timing and Dose Regimens of Marrow Mesenchymal Stem Cell Transplantation Affect the Outcomes and Neuroinflammatory Response After Ischemic Stroke

机译:骨髓间充质干细胞移植的时间和剂量方案影响缺血性卒中的结果和神经炎症反应

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Summary Aims Intravenous transplantation of bone marrow mesenchymal stem cells ( BMSC s) had been documented to improve functional outcome after ischemic stroke. However, the timing and appropriate cell number of transplantation to achieve better outcome after an episode of stroke remain further to be optimized. Methods To determine the optimal conditions, we transplanted different concentrations of BMSC s at different time points in a rat model of ischemic stroke. Infarction volume and neurological behavioral tests were performed after ischemia. Results We found that transplantation of BMSC s at 3 and 24 h, but not 7 days after focal ischemia, significantly reduced the lesion volume and improved motor deficits. We also found that transplanted cells at 1 × 106 to 107, but not at 1 × 104 to 105, significantly improved functional outcome after stroke. In addition to inhibiting macrophages/microglia activation in the ischemic brain, BMSC transplantation profoundly reduced infiltration of gamma delta T ( γδ T) cells, which are detrimental to the ischemic brain, and significantly increased regulatory T cells (Tregs), along with altered Treg‐associated cytokines in the ischemic brain. Conclusions Our data suggest that timing and cell dose of transplantation determine the therapeutic effects after focal ischemia by modulating poststroke neuroinflammation.
机译:概述目的已有文献报道骨髓间充质干细胞(BMSC)的静脉移植可改善缺血性中风后的功能预后。然而,中风发作后的移植时间和适当的细胞数目以获得更好的结果仍有待进一步优化。方法为了确定最佳条件,我们在不同时间点的缺血性中风大鼠模型中移植了不同浓度的BMSC。缺血后进行梗死体积和神经行为学测试。结果我们发现,在局灶性缺血后3天和24小时(而非7天)移植BMSC可以显着减少病变体积并改善运动功能障碍。我们还发现,以1×106至107而不是1×104至105移植的细胞可显着改善中风后的功能结局。除了抑制缺血性脑中的巨噬细胞/小胶质细胞活化外,BMSC移植还大大减少了对缺血性脑有害的γδT细胞(γδT)的浸润,并显着增加了调节性T细胞(Tregs)以及改变的Treg缺血性脑中的相关细胞因子。结论我们的数据表明,移植的时间和细胞剂量可通过调节中风后神经炎症来决定局灶性缺血后的治疗效果。

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