Metabolic Switching, Growth Kinetics and Cell Yields in the Scalable Manufacture of Stem Cell-Derived Insulin-Producing Cells

This publication examines bioprocess parameters and product-quality characteristics during scalable differentiation of human pluripotent stem cells into insulin-producing cells. A seven-stage workflow was performed using planar CellSTACK cultures and PBS-Mini Vertical-Wheel bioreactors. Cells maintained greater than 80% viability and expressed appropriate stage-specific markers throughout differentiation. Cell numbers increased during early stages leading to pancreatic progenitor formation, followed by decreased proliferation and cell loss during endocrine differentiation. Reducing aggregate fusion improved cell yield during later stages. Metabolic analysis identified a progressive shift from glycolysis during early pancreatic development toward oxidative phosphorylation during endocrine differentiation. Glucose consumption and lactate production were proposed as useful attributes for process characterization. The resulting insulin-producing cells responded to several secretagogues, including elevated glucose.