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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Stem/progenitor Cells From Bone Marrow Decrease Neuronal Death In Global Ischemia By Modulation Of Inflammatory/immune Responses
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Stem/progenitor Cells From Bone Marrow Decrease Neuronal Death In Global Ischemia By Modulation Of Inflammatory/immune Responses

机译:骨髓干/祖细胞通过调节炎症/免疫反应来降低全脑缺血中神经元的死亡

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Human mesenchymal stromal cells (hMSCs) were injected into the hippocampus of adult mice 1 day after transient global ischemia. The hMSCs both improved neurologic function and markedly decreased neuronal cell death of the hippocampus. Microarray assays indicated that ischemia up-regulated 586 mouse genes. The hMSCs persisted for <7 days, but they down-regulated >10% of the ischemia-induced genes, most of which were involved in inflammatory and immune responses. The hMSCs also up-regulated three mouse genes, including the neuroprotective gene Ym1 that is expressed by activated microglia/macrophages. In addition, the transcriptomes of the hMSC changed with up-regulation of 170 human genes and down-regulation of 54 human genes. Protein assays of the hippocampus demonstrated increased expression in microglia/macrophages of Ym1, the cell survival factor insulin-like growth factor 1, galectin-3, cytokines reflective of a type 2 T cell immune bias, and the major histocompatibility complex II. The observed beneficial effects of hMSCs were largely explained by their modulation of inflammatory and immune responses, apparently by alternative activation of microglia and/or macrophages.
机译:短暂性全脑缺血后1天,将人间充质基质细胞(hMSCs)注入成年小鼠海马中。 hMSCs既改善了神经功能,又明显减少了海马神经元细胞死亡。微阵列分析表明,缺血上调了586个小鼠基因。 hMSC持续<7天,但它们下调了> 10%的缺血诱导基因,其中大多数与炎症和免疫反应有关。 hMSC还上调了三个小鼠基因,包括由激活的小胶质细胞/巨噬细胞表达的神经保护基因Ym1。另外,hMSC的转录组随着170种人类基因的上调和54种人类基因的下调而改变。海马蛋白测定显示,Ym1,细胞存活因子胰岛素样生长因子1,galectin-3,反映2型T细胞免疫偏倚的细胞因子和主要组织相容性复合物II在小胶质细胞/巨噬细胞中表达增加。观察到的hMSC的有益作用在很大程度上是由于它们对炎症和免疫反应的调节,显然是由小胶质细胞和/或巨噬细胞的选择性激活引起的。

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