Intravenous administration of atorvastatin-pretreated mesenchymal stem cells improves cardiac performance after acute myocardial infarction: role of CXCR4.
Intravenous administration of atorvastatin-pretreated mesenchymal stem cells improves cardiac performance after acute myocardial infarction: role of CXCR4.
复制标题
静脉注射阿托伐他汀预处理的间充质干细胞可改善急性心肌梗死后的心脏功能：CXCR4 的作用。
DOI：
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发表时间：
2015-06
影响因子：
2.2
通讯作者：
Hao Zhang
中科院分区：
文献类型：
--
作者：
Qiu-Ting Dong;Hui Xu;Lei Song;Hao Zhang
背景
基质细胞衍生因子 1 (SDF-1) 与其受体 CXC 趋化因子受体 4 (CXCR4) 之间的相互作用在间充质干细胞 (MSC) 迁移和植入中发挥重要作用。他汀类药物可以增加间充质干细胞的存活率。然而，他汀类药物是否可以增强间充质干细胞的迁移和植入尚不清楚。因此，我们设计本研究来探讨阿托伐他汀（ATV）是否可以增强MSCs的CXCR4表达并促进它们向受损心肌归巢。
方法和结果
通过流式细胞术和实时PCR评估CXCR4的表达。 Transwell系统用于评估MSC的迁移能力。在患有急性心肌梗塞 (AMI) 的 Sprague-Dawley 大鼠中评估了系统输送的 MSC 向梗塞心脏的募集情况。 ATV预处理增强了CXCR4的表达并刺激了MSCs的体外迁移。然而，CXCR4 中和抗体基本上消除了该作用。在 AMI 模型中，我们发现经过 ATV 预处理的 MSC 比未经处理的细胞更多地归巢到梗塞心肌，并且这伴随着心脏功能的改善。
结论
ATV 通过上调 CXCR4 的表达来增加 MSC 的迁移能力并改善心脏功能。这些结果表明，ATV 预处理供体间充质干细胞是提高 AMI 细胞治疗潜力的有效方法。
BACKGROUND
The interaction between stromal cell-derived factor 1 (SDF-1) and its receptor CXC chemokine receptor 4 (CXCR4) plays an important role in mesenchymal stem cells (MSCs) migration and engraftment. Statins can increase the survival of MSCs. However, whether statins could enhance MSCs migration and engraftment is still unknown. Therefore, we designed the study to investigate whether atorvastatin (ATV) could enhance CXCR4 expression of MSCs and promote them homing toward the injured myocardium.
METHODS AND RESULTS
Expression of CXCR4 was evaluated by flow cytometry and real time PCR. A transwell system was used to assess MSCs migration ability. Recruitment of systematically delivered MSCs to the infarcted heart was evaluated in Sprague-Dawley rats with acute myocardial infarction (AMI). ATV pretreatment enhanced the expression of CXCR4 and stimulated MSCs migration in vitro. However, the effect was largely abolished by CXCR4 neutralizing antibody. In AMI models, we found much more ATV-pretreated MSCs homing toward the infarcted myocardium than non-treated cells and this was accompanied by improved cardiac performance.
CONCLUSIONS
ATV increases the migration ability of MSCs and improves cardiac performance due to up-regulated expression of CXCR4. These results suggest that ATV pretreatment of donor MSCs is an effective way to promote cell therapeutic potential for AMI.
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影响因子：
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作者：
Song L;Yang YJ;Dong QT;Qian HY;Gao RL;Qiao SB;Shen R;He ZX;Lu MJ;Zhao SH;Geng YJ;Gersh BJ
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DOI：
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