Early beneficial effects of bone marrow-derived mesenchymal stem cells overexpressing Akt on cardiac metabolism after myocardial infarction.
Early beneficial effects of bone marrow-derived mesenchymal stem cells overexpressing Akt on cardiac metabolism after myocardial infarction.
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DOI：
10.1002/stem.12
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发表时间：
2009-04
期刊：
影响因子：
5.2
通讯作者：
Ingwall, Joanne S.
中科院分区：
文献类型：
--
作者：
Gnecchi, Massimiliano;He, Huamei;Melo, Luis G.;Noiseaux, Nicolas;Morello, Fulvio;de Boer, Rudolf A.;Zhang, Lunan;Pratt, Richard E.;Dzau, Victor J.;Ingwall, Joanne S.
间充质干细胞（MSCs）是一种有效的治疗心肌梗死（MI）后心脏损伤的实验模型。然而，作用机制仍需阐明。我们的小组最近提出，间充质干细胞介导的治疗效果主要是通过旁分泌细胞保护作用。此外，我们已经表明，过表达Akt 1的MSC（Akt-MSC）比未修饰的MSC发挥更大的细胞保护作用。到目前为止，很少有关于用干细胞治疗的梗死心脏的代谢特征的报道。在这里，我们假设Akt-MSC管理可能会影响心肌梗死后心脏适应和修复的代谢过程。在随机分为四组的大鼠中进行MI：假手术组和用对照MSC、Akt-MSC或磷酸盐缓冲溶液（PBS）处理的动物。在MI后72小时和2周，使用磷-31核磁共振波谱法在离体心脏上评价高能代谢和基础2-脱氧葡萄糖（2-DG）摄取。与PBS或MSC处理的动物相比，用Akt-MSC处理节省了磷酸肌酸储存，并显著限制了残留完整心肌中2-DG摄取的增加。此外，Akt-MSC处理的心脏具有正常pH，而在PBS和MSC组中测量到低pH。相关分析表明，MI后功能恢复与2-DG摄取率呈负相关。我们的结论是，管理的MSC过表达Akt在梗死的时间结果在保存正常的代谢和pH值的存活心肌。
Administration of mesenchymal stem cells (MSCs) is an effective therapy to repair cardiac damage after myocardial infarction (MI) in experimental models. However, the mechanisms of action still need to be elucidated. Our group has recently suggested that MSCs mediate their therapeutic effects primarily via paracrine cytoprotective action. Furthermore, we have shown that MSCs overexpressing Akt1 (Akt-MSCs) exert even greater cytoprotection than unmodified MSCs. Thus far, little has been reported on the metabolic characteristics of infarcted hearts treated with stem cells. Here we hypothesize that Akt-MSC administration may influence the metabolic processes involved in cardiac adaptation and repair after MI. MI was performed in rats randomised in four groups: sham group and animals treated with control MSCs, Akt-MSCs or phosphate buffer solution (PBS). High energy metabolism and basal 2-deoxy-glucose (2-DG) uptake were evaluated on isolated hearts using phosphorous-31 nuclear magnetic resonance spectroscopy at 72 hours and two weeks after MI. Treatment with Akt-MSCs spared phosphocreatine stores and significantly limited the increase in 2-DG uptake in the residual intact myocardium compared to the PBS or the MSC treated animals. Furthermore, Akt-MSC treated hearts had normal pH, whereas low pH was measured in the PBS and MSC groups. Correlative analysis indicated that functional recovery after MI was inversely related to the rate of 2-DG uptake. We conclude that administration of MSCs overexpressing Akt at the time of infarction results in preservation of normal metabolism and pH in the surviving myocardium.
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影响因子：
37.8
作者：
Davani, S;Marandin, A;Kantelip, JP
通讯作者：
Kantelip, JP
影响因子：
--
作者：
BAK, MI;INGWALL, JS
通讯作者：
INGWALL, JS
影响因子：
4.8
作者：
Apstein, CS
通讯作者：
Apstein, CS
影响因子：
15.9
作者：
Luptak, Ivan;Shen, Mei;Tian, Rong
通讯作者：
Tian, Rong
DOI：
10.1073/pnas.80.18.5784
发表时间：
1983-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
DEBOER, LWV;RUDE, RE;BRAUNWALD, E
通讯作者：
BRAUNWALD, E