Abstract Mesenchymal stem cells isolated from the Wharton’s jelly of human umbilical cords (WJ-MSC) are of increasing interest for cell therapies, but scalable cell production in stirred tank bioreactors (STR) still requires further investigations in order to be more efficient and with decreased costs. To handle the problem of cell confluence on microcarriers leading to cell aggregation, a new strategy of microcarriers addition was proposed. The ’bead-to-bead transfer’ ability of WJ-MSC was indeed used to maintain constant the number of cells per microcarriers. However, the resulting increase of bead shocks frequency could also negatively impact cell quantity and quality. Until now, no quantitative study describing the impact of bead interactions on WJ-MSC death was reported. In this study the influence of microcarriers addition as well as mixing characteristics on cell viability were determined. Obtained results showed that, when particle mixing is below the just-suspended state condition ( N j s ), local increase of particle volume fraction promotes a significant cell death in an agitation mode of orbital stirring. However, an increase in agitation rate at Njs is clearly beneficial to cell viability and growth. These effects were magnified during microcarrier addition due to the increase of mean volume fraction of particles. The present study also demonstrates the critical influence of Njs and particle distributions within the bioreactor on WJ-MSC culture performances.

中文翻译：

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添加和混合微载体对生物反应器中WJ-MSC培养的影响

摘要 从沃顿氏脐带果冻 (WJ-MSC) 中分离的间充质干细胞对细胞治疗越来越感兴趣，但在搅拌罐生物反应器 (STR) 中可扩展的细胞生产仍需要进一步研究，以提高效率并减少成本。针对细胞在微载体上汇合导致细胞聚集的问题，提出了一种新的微载体添加策略。WJ-MSC 的“珠对珠转移”能力确实用于保持每个微载体的细胞数量恒定。然而，由此产生的珠子冲击频率的增加也会对细胞数量和质量产生负面影响。直到现在，还没有描述磁珠相互作用对 WJ-MSC 死亡影响的定量研究报告。在这项研究中，确定了微载体添加以及混合特性对细胞活力的影响。得到的结果表明，当颗粒混合低于刚悬浮状态条件（N js ）时，颗粒体积分数的局部增加促进了轨道搅拌搅拌模式下的显着细胞死亡。然而，Njs 搅拌速率的增加显然有利于细胞活力和生长。由于颗粒平均体积分数的增加，这些影响在微载体添加过程中被放大。本研究还证明了生物反应器内 Njs 和颗粒分布对 WJ-MSC 培养性能的关键影响。当粒子混合低于刚悬浮状态条件 (N js ) 时，粒子体积分数的局部增加会在轨道搅拌的搅拌模式下促进显着的细胞死亡。然而，Njs 搅拌速率的增加显然有利于细胞活力和生长。由于颗粒平均体积分数的增加，这些影响在微载体添加过程中被放大。本研究还证明了生物反应器内 Njs 和颗粒分布对 WJ-MSC 培养性能的关键影响。当粒子混合低于刚悬浮状态条件 (N js ) 时，粒子体积分数的局部增加会在轨道搅拌的搅拌模式下促进显着的细胞死亡。然而，Njs 搅拌速率的增加显然有利于细胞活力和生长。由于颗粒平均体积分数的增加，这些影响在微载体添加过程中被放大。本研究还证明了生物反应器内 Njs 和颗粒分布对 WJ-MSC 培养性能的关键影响。由于颗粒平均体积分数的增加，这些影响在微载体添加过程中被放大。本研究还证明了生物反应器内 Njs 和颗粒分布对 WJ-MSC 培养性能的关键影响。由于颗粒平均体积分数的增加，这些影响在微载体添加过程中被放大。本研究还证明了生物反应器内 Njs 和颗粒分布对 WJ-MSC 培养性能的关键影响。