Synchronized mammalian cell culture: Part II—population ensemble modeling and analysis for development of reproducible processes
Synchronized mammalian cell culture: Part II—population ensemble modeling and analysis for development of reproducible processes
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同步哺乳动物细胞培养：第二部分：群体整体建模和分析，用于开发可重复的过程
DOI：
10.1002/btpr.2006
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发表时间：
2015
影响因子：
2.9
通讯作者：
Pörtner
中科院分区：
文献类型：
--
作者：
Platas Barradas;Pörtner
考虑哺乳动物细胞培养的固有群体不均一性对于系统生物学研究和开发更稳定和有效的过程变得越来越重要。然而，属于不同亚群的细胞特性的变化及其对细胞生理学和生物生产条件下培养生产力动力学的潜在影响尚未成为研究的焦点。培养物的异质性在很大程度上取决于细胞周期的进展。根据在其他生理条件下的（部分）同步培养和随后的群体分辨模型调整的组合，可以最佳地确定细胞周期特异性细胞变异对大规模工艺条件的分配。第一步已经实现了使用逆流离心淘洗的物理选择方法，最近在我们的小组建立了不同的哺乳动物细胞系，这是在本文系列的第一部分。在第二部分中，我们展示了细胞周期依赖性群体平衡系综模型的成功适应和应用，以描述和理解用两种模型哺乳动物细胞系AGE1.HNAAT和CHO-K1进行的同步生物反应器培养。模型对实验数据的数值适应允许检测阶段特异性参数，并确定不同阶段和不同细胞系之间的显著变化。它表明，必须特别注意在这种振荡文化的采样频率，以尽量减少相移（抖动）的文物。基于对取决于其起始条件的培养物的长期振荡行为的预测，提出了高细胞产量和高同步效率之间的最佳淘析设置权衡。© 2014美国化学工程师学会Biotechnol。程序：31：175-185，2015
The consideration of inherent population inhomogeneities of mammalian cell cultures becomes increasingly important for systems biology study and for developing more stable and efficient processes. However, variations of cellular properties belonging to different sub‐populations and their potential effects on cellular physiology and kinetics of culture productivity under bioproduction conditions have not yet been much in the focus of research. Culture heterogeneity is strongly determined by the advance of the cell cycle. The assignment of cell‐cycle specific cellular variations to large‐scale process conditions can be optimally determined based on the combination of (partially) synchronized cultivation under otherwise physiological conditions and subsequent population‐resolved model adaptation. The first step has been achieved using the physical selection method of countercurrent flow centrifugal elutriation, recently established in our group for different mammalian cell lines which is presented in Part I of this paper series. In this second part, we demonstrate the successful adaptation and application of a cell‐cycle dependent population balance ensemble model to describe and understand synchronized bioreactor cultivations performed with two model mammalian cell lines, AGE1.HNAATand CHO‐K1. Numerical adaptation of the model to experimental data allows for detection of phase‐specific parameters and for determination of significant variations between different phases and different cell lines. It shows that special care must be taken with regard to the sampling frequency in such oscillation cultures to minimize phase shift (jitter) artifacts. Based on predictions of long‐term oscillation behavior of a culture depending on its start conditions, optimal elutriation setup trade‐offs between high cell yields and high synchronization efficiency are proposed. © 2014 American Institute of Chemical EngineersBiotechnol. Prog., 31:175–185, 2015
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影响因子：
--
作者：
Platas Barradas O;Jandt U;Hass R;Kasper C;Sandig V;Pörtner R;Zeng AP
通讯作者：
Zeng AP
影响因子：
2.1
作者：
A. Groh;J. Krebs;M. Wagner
通讯作者：
M. Wagner
影响因子：
--
作者：
Zhou X;Kerkhof M;Span L;Friedrich A;Arends J
通讯作者：
Arends J
影响因子：
2.9
作者：
Liu, Yuan-Hua;Bi, Jing-Xiu;Yuan, Jing-Qi
通讯作者：
Yuan, Jing-Qi
影响因子：
2.4
作者：
Solinas S;Colnaghi T;D'Angelo E
通讯作者：
D'Angelo E