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 “naïve” 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 naïve-like pluripotent state. Our research corroborates that converting hPSCs towards a naïve state enhances hPSC manufacturing and indicates a potentially important role for the stirred suspension bioreactor’s mechanical environment in maintaining naïve-like pluripotency.

由于它们能够标准化关键生理参数，搅拌悬浮生物反应器可以潜在地扩大用于细胞治疗应用的质量控制的多能干细胞 (PSC) 的生产。由于小鼠 (m) 和人 (h) PSC 之间生物反应器扩增效率的差异，我们研究了 hPSC 从传统的“引发”多能状态向 mPSC 中普遍存在的“初始”状态的转化是否可用于增强 hPSC生产。通过机械传感信号的转录组学富集、表观遗传调节因子的表达、代谢组学和细胞表面蛋白标记分析，我们表明搅拌悬浮生物反应器环境有助于维持幼稚的多能状态。