Abstract To scale-up a filling process in a cell manufacturing system, the impact of the processing time on the final product quality should be evaluated. It is known that the suspended cells in a cryopreservation solution are subjected to various types of stress factors, which eventually results in apoptotic or necrotic death. In this study, the aim was to investigate a critical factor of cell decay in human induced pluripotent stem cells suspended in a cryopreservation solution and to propose a methodology to maintain the viability of cells for a longer filling process time. Based on experimental results, it was determined that the accumulation of intracellular reactive oxygen species induces apoptosis of cells suspended in a cryopreservation solution. In addition, treatment with an antioxidant or a low-temperature condition was effective in suppressing the induction of apoptosis and subsequent cell death. In particular, the treatment at low temperature was able to maintain the attachment efficiency of suspended cells at a higher level compared to the treatment with antioxidants. The appropriate control of redox balance in cells suspended in a cryopreservation solution could improve the viability of cells in the filling process and lead to the successful lot size expansion of cell manufacturing systems.

中文翻译：

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通过控制悬浮在冷冻保存溶液中的人诱导多能干细胞的氧化还原平衡抑制时间依赖性衰变

摘要 为了扩大电池制造系统中的填充工艺，应评估加工时间对最终产品质量的影响。众所周知，冷冻保存液中的悬浮细胞会受到各种应激因素的影响，最终导致细胞凋亡或坏死。在这项研究中，目的是研究悬浮在冷冻保存溶液中的人类诱导多能干细胞中细胞衰变的关键因素，并提出一种方法，以在更长的填充过程中保持细胞的活力。根据实验结果，确定细胞内活性氧的积累会诱导悬浮在冷冻保存液中的细胞凋亡。此外，用抗氧化剂或低温条件处理可有效抑制细胞凋亡的诱导和随后的细胞死亡。特别是，与抗氧化剂处理相比，低温处理能够将悬浮细胞的附着效率保持在更高的水平。适当控制悬浮在冷冻保存溶液中的细胞中的氧化还原平衡可以提高细胞在填充过程中的活力，并导致细胞制造系统的批量扩大成功。