Increased oxygen consumption and OXPHOS potential in superhealer mesenchymal stem cells

摘要

Background Cell-based therapies show promise in repairing cardiac tissue and improving contractile performance following a myocardial infarction. Despite this, ischemia-induced death of transplanted cells remains a major hurdle to the efficacy of treatment. ‘Superhealer’ MRL/MpJ mesenchymal stem cells (MRL-MSCs) have been reported to exhibit increased engraftment resulting in reduced infarct size and enhanced contractile function. This study determines whether intrinsic differences in mitochondrial oxidative phosphorylation (OXPHOS) assist in explaining the enhanced cellular survival and engraftment of MRL-MSCs. Findings Compared to wild type MSCs (WT-MSCs), mitochondria from intact MRL-MSCs exhibited an increase in routine 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 spare respiratory capcity. Additionally, glutamate/malate- and succinate-supported oxygen consumption in permeabilized cells was elevated approximately 1.25- and 1.4-fold in the MRL-MSCs, respectively. Conclusion The results from intact and permeabilized MSCs indicate MRL-MSCs exhibit a greater reliance on and capacity for aerobic metabolism. The greater capacity for oxidative metabolism may provide a protective effect by increasing ATP synthesis per unit substrate and prevent glycolysis-mediated acidosis and subsequent cell death upon transplantation into the glucose-and oxygen-deprived environment of the infarcted heart.