Stirred suspension bioreactors maintain naive pluripotency of human pluripotent stem cells

Due to their ability to standardize key physiological parameters, stirred suspension bioreactors can potentially scale the production of quality-controlled pluripotent stem cells (PSCs) for cell therapy application. Because of differences in bioreactor expansion efficiency between mouse (m) and human (h) PSCs, we investigated if conversion of hPSCs, from the conventional primed pluripotent state towards the naive state prevalent in mPSCs, could be used to enhance hPSC production. Through transcriptomic enrichment of mechano-sensing signaling, the expression of epigenetic regulators, metabolomics, and cell-surface protein marker analyses, we show that the stirred suspension bioreactor environment helps maintain a naive-like pluripotent state. Our research corroborates that converting hPSCs towards a naive state enhances hPSC manufacturing and indicates a potentially important role for the stirred suspension bioreactor's mechanical environment in maintaining naive-like pluripotency. Rohani et al show that converting human pluripotent stem cells (hPSCs) to the naive state enhances hPSC manufacturing. Further, through transcriptomics, the expression of epigenetic regulators, metabolomics, and cell-surface protein marker analyses, they indicate a potentially important role for the stirred bioreactor's mechanical environment in maintaining naive-like pluripotency.