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Early Beneficial Effects of Bone Marrow‐Derived Mesenchymal Stem Cells Overexpressing Akt on Cardiac Metabolism After Myocardial Infarction
Author(s) -
Gnecchi Massimiliano,
He Huamei,
Melo Luis G.,
Noiseux Nicolas,
Morello Fulvio,
de Boer Rudolf A.,
Zhang Lunan,
Pratt Richard E.,
Dzau Victor J.,
Ingwall Joanne S.
Publication year - 2009
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.12
Subject(s) - mesenchymal stem cell , protein kinase b , biology , stem cell , pi3k/akt/mtor pathway , myocardial infarction , pharmacology , medicine , endocrinology , cancer research , apoptosis , microbiology and biotechnology , biochemistry
Abstract 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. S TEM CELLS 2009;27:971–979

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