Stem Cell Metabolism: Powering Cell-Based Therapeutics

Cell-based therapeutics for cardiac repair have been extensively used during the last decade. Preclinical studies have demonstrated the effectiveness of adoptively transferred stem cells for enhancement of cardiac function. Nevertheless, several cell-based clinical trials have provided largely underwhelming outcomes. A major limitation is the lack of survival in the harsh cardiac milieu as only less than 1% donated cells survive. Recent efforts have focused on enhancing cell-based therapeutics and understanding the biology of stem cells and their response to environmental changes. Stem cell metabolism has recently emerged as a critical determinant of cellular processes and is uniquely adapted to support proliferation, stemness, and commitment. Metabolic signaling pathways are remarkably sensitive to different environmental signals with a profound effect on cell survival after adoptive transfer. Stem cells mainly generate energy through glycolysis while maintaining low oxidative phosphorylation (OxPhos), providing metabolites for biosynthesis of macromolecules. During commitment, there is a shift in cellular metabolism, which alters cell function. Reprogramming stem cell metabolism may represent an attractive strategy to enhance stem cell therapy for cardiac repair. This review summarizes the current literature on how metabolism drives stem cell function and how this knowledge can be applied to improve cell-based therapeutics for cardiac repair.