Mammalian cell culture synchronization under physiological conditions and population dynamic simulation

Mammalian cell culture synchronization under physiological conditions and population dynamic simulation
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生理条件下哺乳动物细胞培养同步及群体动态模拟

DOI:
10.1007/s00253-014-5553-6
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发表时间:
2014
影响因子:
5
通讯作者:
Pörtner
Pörtner
中科院分区:
工程技术2区
文献类型:
--
作者:
Platas Barradas;Pörtner

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细胞培养物的总体行为由所有细胞的行为和调节以及它们在混合群体中的相互作用决定。然而,在细胞培养过程的研究中,由培养物内的多样性和异质性引起的动力学常常被忽视。通常,假定为整体行为,尽管在大多数情况下不均匀性占主导地位。然而,从整体行为到单细胞行为的结论是无效的。相反,有必要将亚群的行为和动力学及其相互作用纳入模型,以阐明典型细胞培养中发生的动态效应。细胞培养中的异源性很大程度上是由细胞周期的进展引起的。细胞周期依赖性动力学导致例如可变的转染效率或表达双稳态最近引起了关注。为了阐明细胞培养物中的细胞周期依赖性调节,期望使培养物与最小扰动同步,这对于使用物理方法的不同产量和质量是可能的,但对于经常使用的化学或全培养方法是不可能的。然后,在生理条件下再次培养培养物,并应用亚群分辨分析和建模方法。这应该允许帐户的变量贡献的亚群的整体行为,也为获得迄今为止无法访问的动态信息的细胞调节。在这篇简短的综述中,我们总结了成功的同步化,培养和建模,以实现更好地理解细胞培养的目标,在人口水平上的技术和关键问题要考虑。
The overall behavior of cell cultures is determined by the actions and regulations of all cells and their interaction in a mixed population. However, the dynamics caused by diversity and heterogeneity within cultures is often neglected in the study of cell culture processes. Usually, a bulk behavior is assumed, although heterogeneity prevails in most cases. It is, however, not valid to conclude from the bulk behavior to the single cell behavior. Instead, it is necessary to include the behavior and kinetics of subpopulations and their interactions into models in order to elucidate the dynamic effects occurring in typical cell cultures. Heterogeneity in cell cultures is largely caused by the progress of the cell cycle. Cell cycle-dependent dynamics resulting for example in variable transfection efficiencies or expression bistability have recently attracted attention. In order to elucidate cell cycle-dependent regulations in cell cultures, it is desirable to synchronize a culture with minimal perturbation, which is possible with different yield and quality using physical methods, but not possible for frequently used chemical, or whole-culture methods. Then, the culture is cultivated again under physiological conditions and subpopulation-resolved analysis and modeling approaches are applied. This should allow to account for the variable contributions of subpopulations to the whole behavior and also for obtaining hereto unaccessible dynamic information of cellular regulation. In this short review, we summarize techniques and key issues to be considered for successful synchronization, cultivation, and modeling in order to achieve the goal of better understanding cell culture at a population level.
DOI: --
发表时间: 2005
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期刊: BMC proceedings
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标准化摇匀以同步培养的 CHO 细胞。
DOI: --
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