Effects of Mesenchymal Stem Cell Treatment on the Expression of Matrix Metalloproteinases and Angiogenesis during Ischemic Stroke Recovery.
Effects of Mesenchymal Stem Cell Treatment on the Expression of Matrix Metalloproteinases and Angiogenesis during Ischemic Stroke Recovery.
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DOI：
10.1371/journal.pone.0144218
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Heo JH
中科院分区：
文献类型：
--
作者：
Nam HS;Kwon I;Lee BH;Kim H;Kim J;An S;Lee OH;Lee PH;Kim HO;Namgoong H;Kim YD;Heo JH
间充质干细胞（MSC）移植治疗缺血性中风的疗效可能取决于给药时机。我们研究了MSC移植的最佳时间点。 MSC 治疗后，我们还研究了在血管和组织重塑中发挥作用的基质金属蛋白酶 (MMP) 的表达。在雄性 Sprague-Dawley 大鼠中诱导永久性大脑中动脉闭塞 (MCAO) 后，静脉注射人骨髓来源的 MSC（2 × 106，第 5 代）。首先，我们确定了 MCAO 后 1 小时、1 天和 3 天神经功能最大恢复的 MSC 移植时间点。接下来，我们测量了移植 MSC 后神经功能最大程度恢复时 MMP-2 和 MMP-9 的活性、神经功能恢复、梗塞体积和血管密度。在MSC移植的大鼠中，MSC 1小时组的大鼠在转棒试验（P = 0.023）和Longa评分（P = 0.018）中表现出最大程度的恢复。 MSC 1小时组MCAO后第1天的MMP-2活性显着高于对照组（P = 0.002），但MMP-9活性不明显。与对照组相比，MSC 1 小时组还显示出更小的梗塞体积和更高的血管密度。在啮齿类 MCAO 的永久性模型中，人类 MSC 的早期移植（MCAO 后 1 小时）可产生更好的神经功能恢复并减少梗塞体积。 MSC治疗后MMP-2活性的升高和血管密度的增加表明MSC可能有助于促进血管生成并导致缺血性中风后恢复阶段的神经功能改善。
The efficacy of mesenchymal stem cell (MSC) transplantation in ischemic stroke might depend on the timing of administration. We investigated the optimal time point of MSC transplantation. After MSC treatment, we also investigated the expression of matrix metalloproteinases (MMPs), which play a role in vascular and tissue remodeling. Human bone marrow-derived MSCs (2 × 106, passage 5) were administrated intravenously after permanent middle cerebral artery occlusion (MCAO) was induced in male Sprague-Dawley rats. First, we determined the time point of MSC transplantation that led to maximal neurological recovery at 1 h, 1 day, and 3 days after MCAO. Next, we measured activity of MMP-2 and MMP-9, neurological recovery, infarction volume, and vascular density after transplanting MSCs at the time that led to maximal neurological recovery. Among the MSC-transplanted rats, those of the MSC 1-hour group showed maximal recovery in the rotarod test (P = 0.023) and the Longa score (P = 0.018). MMP-2 activity at 1 day after MCAO in the MSC 1-hour group was significantly higher than that in the control group (P = 0.002), but MMP-9 activity was not distinct. The MSC 1-hour group also showed smaller infarction volume and higher vascular density than did the control group. In a permanent model of rodent MCAO, very early transplantation of human MSCs (1 h after MCAO) produced greater neurological recovery and decreased infraction volume. The elevation of MMP-2 activity and the increase in vascular density after MSC treatment suggest that MSCs might help promote angiogenesis and lead to neurological improvement during the recovery phase after ischemic stroke.