Cardiosphere-Derived Cells Demonstrate Metabolic Flexibility That Is Influenced by Adhesion Status

Highlights •Cell adhesion status regulates energy metabolism in adult stem cells •Adherent adult stem cells (CDCs, MSCs, ASCs) utilize glycolysis to generate majority (70% to 85%) of their cellular ATP needs •Akt phosphorylation transduces adhesion-mediated regulation of energy metabolism by regulating membrane translocation of glucose transporters (GLUT1) and thus, cellular glucose uptake and glycolysis •Cell dissociation/suspension leads to Akt de-phosphorylation, >3-fold reduction in the number of cell surface GLUT1 receptors, downregulation of cellular glucose uptake, glycolysis, cellular ATP levels, and loss of cell viability •Encapsulation of dissociated cells in hydrogels that provide cell adhesion motifs, promotes Akt phosphorylation, rapidly restores glycolysis, and cellular ATP levels • 99m Tc-pertechnetate uptake (by cells genetically engineered to express the Na-Iodide symporter) reflects cellular ATP levels, thus permitting in vivo monitoring of energetics of transplanted cells by SPECT imaging.