Early Beneficial Effects of Bone Marrow-Derived Mesenchymal Stem Cells Overexpressing Akt on Cardiac Metabolism After Myocardial Infarction

被引:97
作者
Gnecchi, Massimiliano [1 ,4 ,5 ]
He, Huamei [2 ,3 ]
Melo, Luis G. [1 ]
Noiseaux, Nicolas [1 ]
Morello, Fulvio [1 ]
de Boer, Rudolf A. [1 ]
Zhang, Lunan [1 ]
Pratt, Richard E. [1 ]
Dzau, Victor J. [1 ]
Ingwall, Joanne S. [2 ,3 ]
机构
[1] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA
[2] Harvard Univ, Sch Med, Boston, MA USA
[3] Brigham & Womens Hosp, Dept Med, NMR Lab Physiol Chem, Boston, MA 02115 USA
[4] Univ Pavia, Dept Heart Blood & Lung, I-27100 Pavia, Italy
[5] Fdn IRCCS Policlin San Matteo, Dept Heart Blood & Lung, Lab Expt Cardiol Cell & Mol Therapy, I-27100 Pavia, Italy
基金
美国国家卫生研究院;
关键词
Metabolism; Glucose uptake; Paracrine effect; Mesenchymal stem cell; Myocardial infarction; INCREASED GLYCOLYTIC SUBSTRATE; CORONARY-OCCLUSION; ISCHEMIC-HEART; STROMAL CELLS; CREATINE; PROTECTION; ACTIVATION; MECHANISMS; GROWTH; DEATH;
D O I
10.1002/stem.12
中图分类号
Q813 [细胞工程];
学科分类号
摘要
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. So 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 randomized in four groups: sham group and animals treated with control MSCs, Akt-MSCs, or phosphate-buffered saline (PBS). High energy metabolism and basal 2-deoxy-glucose (2-DG) uptake were evaluated on isolated hearts using phosphorus-31 nuclear magnetic resonance spectroscopy at 72 hours and 2 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 with 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. STEM CELLS 2009;27:971-979
引用
收藏
页码:971 / 979
页数:9
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