Increased oxygen consumption and OXPHOS potential in superhealer mesenchymal stem cells

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 succinate-supported oxygen consumption in permeabilized cells was elevated approximately 1.25- and 1.4-fold in the MRL-MSCs, respectively.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.Advances in stem cell therapy for treating a myocardial infarction (MI) are impeded by inadequate survival and engraftment of implanted cells in the host tissue. Up to 99% of mesenchymal stem cells (MSCs) experience cell death following administration into the infarcted heart [1,2]. A predominant factor for the poor survival is ischemia [3,4]. Ischemia results in ATP depletion, a reduction in mitochondrial oxidative phosphorylation (OXPHOS) and increased reliance on glycolysis leading to cellular acidosis and cell death [4].The bone-marrow derived ‘Superhealer’ MRL/MpJ MSC (MRL-MSC) has been reported to exhibit greater engraftment in the infarcted heart [5]. This improved retention promotes superior cardio-protection as indicated by increased angiogenesis, reduced infarct size and improved contractility in a murine MI model [5]. The primary contributor of MRL-MSC-mediated wound repair and cardiac contractile improvements was identified as the paracrine/autocrine factor, secreted frizzled related receptor protein 2 (sFRP2) [5,6]. sFRP2 is a member of the sFRP