Metabolic profiling reveals that time related physiological changes in mammalian cell perfusion cultures are bioreactor scale independent
Metabolic profiling reveals that time related physiological changes in mammalian cell perfusion cultures are bioreactor scale independent
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DOI：
10.1016/j.ymben.2013.04.005
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发表时间：
2013-09-01
影响因子：
8.4
通讯作者：
Klapa, Maria I.
中科院分区：
文献类型：
--
作者：
Vernardis, Spyros I.;Goudar, Chetan T.;Klapa, Maria I.
在实验室和生产规模的哺乳动物细胞灌注培养中，代谢谱被用来描述细胞生理学的时间过程。两项独立实验涉及来自同一BHK细胞库的三个小瓶，用于接种三个实验室规模的生物反应器，其中四个生产规模的培养开始。结果表明，代谢组学分析确实可以通过提供更高分辨率的代谢状态视图来增强监测灌注培养的主要变量数据集。代谢谱可以捕捉灌注培养过程中的生理状态变化，并表明相变的代谢“特征”，这是无法从主要变量数据中观察到的。具体来说，绝大多数代谢物在中间阶段的浓度低于其他两个阶段。值得注意的是，代谢组学提供了正交（与主要变量）的证据，表明所有培养物都遵循相同的代谢状态变化，与细胞年龄无关，与生物反应器规模无关。(C) 2013爱思唯尔公司版权所有。
Metabolic profiling was used to characterize the time course of cell physiology both in laboratory- and manufacturing-scale mammalian cell perfusion cultures. Two independent experiments were performed involving three vials from the same BHK cell bank, used to inoculate three laboratory-scale bioreactors, horn which four manufacturing-scale cultures were initiated It was shown that metabolomic analysis can indeed enhance the prime variable dataset for the monitoring of perfusion cultures by providing a higher resolution view of the metabolic state. Metabolic profiles could capture physiological state shifts over the course of the perfusion cultures and indicated a metabolic "signature" of the phase transitions, which was not observable from prime variable data. Specifically, the vast majority of metabolites had lower concentrations in the middle compared to the other two phases. Notably, metabolomics provided orthogonal (to prime variables) evidence that all cultures followed this same metabolic state shift with cell age, independently of bioreactor scale. (C) 2013 Elsevier Inc. All rights reserved.