Process Engineering of Stem Cell Metabolism for Large-Scale Expansion and Differentiation in Bioreactors

Mesenchymal stem cells (MSCs) and pluripotent stem cells (PSCs) emerge as promising tools for tissue engineering, cell therapy, and drug screening.  Their potential use in clinical applications requires the efficient production of differentiated cells at large scale. Glucose, amino acid, and oxygen metabolism play a key role in MSC and PSC expansion and differentiation. The efficient expansion of stem cells is found to rely on glycolysis, while during differentiation stem cells shift their metabolic pathway to oxidative phosphorylation. During reprogramming, the reverse metabolic shift from oxidative phosphorylation to glycolysis is observed.  As a consequence, the demands for glucose and oxygen vary upon different phases of stem cell production.  Accurate understanding of stem cell metabolism is critical for the rational design of culture parameters such as oxygen tension and feeding regime in bioreactors towards efficient integrated expansion and differentiation processes at large scale.  This presentation discusses current understanding of MSC and PSC metabolism during expansion and differentiation as well as the emerging role of metabolic plasticity in pluripotent stem cell reprogramming.  In addition, the translational potential of incorporating stem cell metabolism into the design of efficient culture processes in bioreactors is discussed towards mass production of stem cell-derived therapeutics.