Ohtaki Hirokazu, Ylostalo Joni H, Foraker Jessica E, Robinson Andrew P, Reger Roxanne L, Shioda Seiji, Prockop Darwin J
Center for Gene Therapy, Tulane University Health Sciences Center, New Orleans, LA 70112, USA.
Proc Natl Acad Sci U S A. 2008 Sep 23;105(38):14638-43. doi: 10.1073/pnas.0803670105. Epub 2008 Sep 15.
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.
在短暂性全脑缺血1天后，将人间充质基质细胞（hMSCs）注射到成年小鼠的海马体中。hMSCs既能改善神经功能，又能显著减少海马体中的神经元细胞死亡。基因芯片分析表明，缺血使586个小鼠基因上调。hMSCs持续存在时间不足7天，但它们使超过10%的缺血诱导基因下调，其中大多数基因参与炎症和免疫反应。hMSCs还上调了三个小鼠基因，包括由活化的小胶质细胞/巨噬细胞表达的神经保护基因Ym1。此外，hMSCs的转录组发生了变化，170个人类基因上调，54个人类基因下调。海马体的蛋白质分析表明，小胶质细胞/巨噬细胞中Ym1、细胞存活因子胰岛素样生长因子1、半乳糖凝集素-3、反映2型T细胞免疫偏向的细胞因子以及主要组织相容性复合体II的表达增加。hMSCs观察到的有益作用很大程度上是由于它们对炎症和免疫反应的调节，显然是通过小胶质细胞和/或巨噬细胞的替代性激活实现的。
