Mesenchymal Stem Cell Treatment Prevents Post-Stroke Dysregulation of Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases
Mesenchymal Stem Cell Treatment Prevents Post-Stroke Dysregulation of Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases
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DOI：
10.1159/000485533
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发表时间：
2017-01-01
影响因子：
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通讯作者：
Veeravalli, Krishna Kumar
中科院分区：
文献类型：
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作者：
Chelluboina, Bharath;Nalamolu, Koteswara Rao;Veeravalli, Krishna Kumar
背景/目的：干细胞治疗是缺血性卒中的潜在治疗选择之一。我们最近证明了人脐带血来源的间充质干细胞（HUCB-MSCs）在缺血性中风大鼠模型中的保护作用。该处理减弱了细胞凋亡并防止了DNA损伤。一系列已发表的研究，包括我们实验室的几项研究，表明了几种基质金属蛋白酶（MMPs）在卒中后脑损伤中的诱导和有害作用。我们假设局灶性脑缺血后HUCB-MSCs治疗可以防止MMPs的失调，并诱导内源性金属蛋白酶组织抑制剂（TIMPs）的表达，以中和MMPs的活性升高。研究方法：为了验证我们的假设，我们通过尾静脉向雄性Sprague-Dawley大鼠静脉内施用HUCB-MSC（0.25百万个细胞/动物和1百万个细胞/动物），所述雄性Sprague-Dawley大鼠经受短暂的（两小时）右侧大脑中动脉闭塞（MCAO）和一天的再灌注。再灌注7天后从各组大鼠获得的缺血脑组织进行实时PCR、免疫印迹和免疫荧光分析。结果：HUCB-MSCs治疗阻止了MMPs的诱导，MMPs在未接受治疗的缺血诱导大鼠中上调。HUCB-MSC处理也阻止了TIMPs表达的诱导。HUCB-MSC治疗对MMP和TIMP诱导的预防程度在两种测试剂量下相似。结论：HUCB-MSCs治疗后对卒中诱导的MMPs上调的预防不是通过TIMPs上调介导的。(c)2017作者（s）由S. Karger AG，巴塞尔
Background/Aims: Stem cell treatment is one of the potential treatment options for ischemic stroke. We recently demonstrated a protective effect of human umbilical cord blood-derived mesenchymal stem cells (HUCB-MSCs) in a rat model of ischemic stroke. The treatment attenuated apoptosis and prevented DNA damage. A collection of published studies, including several from our laboratory, indicated the induction and detrimental role for several matrix metalloproteinases (MMPs) in post-stroke brain injury. We hypothesized that the HUCB-MSCs treatment after focal cerebral ischemia prevents the dysregulation of MMPs and induces the expression of endogenous tissue inhibitors of metalloproteinases (TIMPs) to neutralize the elevated activity of MMPs. Methods: To test our hypothesis, we administered HUCB-MSCs (0.25 million cells/animal and 1 million cells/animal) intravenously via tail vein to male Sprague-Dawley rats that were subjected to a transient (two-hour) right middle cerebral artery occlusion (MCAO) and one-day reperfusion. Ischemic brain tissues obtained from various groups of rats seven days after reperfusion were subjected to real-time PCR, immunoblot, and immunofluorescence analysis. Results: HUCB-MSCs treatment prevented the induction of MMPs, which were upregulated in ischemia-induced rats that received no treatment. HUCB-MSCs treatment also prevented the induction of TIMPs expression. The extent of prevention of MMPs and TIMPs induction by HUCB-MSCs treatment is similar at both the doses tested. Conclusion: Prevention of stroke-induced MMPs upregulation after HUCB-MSCs treatment is not mediated through TIMPs upregulation. (c) 2017 The Author(s) Published by S. Karger AG, Basel