Abstract
ObjectiveIschemia‐induced death impedes the efficacy of cell‐based therapies in the treatment of a myocardial infarction. Superhealer MRL/MpJ mesenchymal stem cells (MRL‐MSCs) exhibit increased engraftment resulting in reduced infarct size and enhanced contractile function.Methods and ResultsHigh resolution respirometry was employed to evaluate differences in mitochondrial oxidative phosphorylation that explain the enhanced cellular survival and engraftment of MRL‐MSCs. Compared to wild type MSCs, MRL‐MSCs exhibited an increase in physiological respiration and maximal electron transport capacity by 2.0‐ and 3.5‐fold, respectively. When routine oxygen utilization is expressed as a portion of maximal cellular oxygen flux, the MRL‐MSCs have a greater energetic reserve. Additionally, succinate‐supported oxygen consumption is elevated 1.4‐fold in the MRL‐MSCs.ConclusionMRL‐MSCs exhibit a greater reliance on and capacity for aerobic metabolism. These characteristics may diminish cell death upon transplantation into the infarcted heart by increasing ATP synthesis per unit substrate and preventing glycolysis‐mediated acidosis. This work was supported by CIHR, AHFMR, CDA, HSF and NIH Grant [R01‐ HL088424].
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