Early beneficial effects of bone marrow-derived mesenchymal stem cells overexpressing akt on cardiac metabolism after myocardial infarction

Massimiliano Gnecchi, Huamei He, Luis G. Melo, Nicolas Noiseaux, Fulvio Morello, Rudolf A. De Boer, Lunan Zhang, Richard E. Pratt, Victor J. Dzau, Joanne S. Ingwall

Research output: Contribution to journalArticlepeer-review

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 MSCtreated 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.

Original languageEnglish
Pages (from-to)971-979
Number of pages9
JournalStem Cells
Volume27
Issue number4
DOIs
Publication statusPublished - Apr 2009

Keywords

  • Glucose uptake
  • Mesenchymal stem cell
  • Metabolism
  • Myocardial infarction
  • Paracrine effect

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Molecular Medicine

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