Development of a scalable suspension culture for cardiac differentiation from human pluripotent stem cells

摘要: To meet the need of a large quantity hPSC-derived cardiomyocytes (CM) for pre-clinical and clinical studies, robust scalable differentiation system CM production is essential. With human pluripotent stem cells (hPSC) aggregate suspension culture we established previously, developed matrix-free, scalable, GMP-compliant process directing hPSC to in by modulating Wnt pathways with small molecules. By optimizing critical parameters including: cell size, molecule concentrations, induction timing, agitation rate, were able consistently differentiate hPSCs >90% purity an average yield 1.5 2×10(9) CM/L at scales up 1L spinner flasks. generated from displayed typical genetic, morphological, electrophysiological cardiac characteristics. This allows seamless transition expansion continuous culture. It not only provides cost labor effective scale production, but also bioreactor prototype automation manufacturing, which will accelerate advance research towards therapeutic applications.