Engineering Characterization of Small-Scale Bioreactors for Large-Scale hiPSC Production.

Human induced pluripotent stem cells (hiPSC) have great potential for cell therapy applications. To meet the global demand for hiPSC-derived cell therapies, the implementation of scalable technologies, such as stirred-tank bioreactors (STB), is essential. However, the addition of physical cues, including shear stress, can impact cell viability and proliferation and requires precise tuning. In this work, we used an engineering characterization approach to estimate the impeller power number (0.5) and investigate the mixing and suspension dynamics in the first generation of small-scale (0.2 L) DASGIP bioreactors (DASGIP-STB). By keeping constant power input per volume (P/V = 4.6 W/m) as a scale-up criteria, we successfully transferred a hiPSC expansion process to a 0.2 L single-use STB (BioBLU-STB) and scaled it up to a single-use 2 L STB (Univessel-STB) without compromising cell expansion, viability, and metabolism, as well as hiPSC quality attributes, including their pluripotent phenotype and differentiation potential.