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首页> 外文期刊>Biotechnology Progress >Segregated Mathematical Model for Growth of Anchorage-Dependent MDCK Cells in Microcarrier Culture
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Segregated Mathematical Model for Growth of Anchorage-Dependent MDCK Cells in Microcarrier Culture

机译：微载体培养中锚定依赖性MDCK细胞生长的分离数学模型

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摘要

To describe the growth behavior of anchorage-dependent mammalian cells in microcarrier systems,various approaches comprising deterministic and stochastic single cell models as well as automaton-based models have been presented in the past.The growth restriction of these often contact-inhibited cells by spatial effects is described at levels with different complexity but for the most part not taking into account their metabolic background.Compared to suspension cell lines these cells have a comparatively long lag phase required for attachment and start of proliferation on the microcarrier.After an initial phase of exponential growth only a moderate specific growth rate is achieved due to restrictions in space available for cell growth,limiting medium components,and accumulation of growth inhibitors.Here,a basic deterministic unstructured segregated cell model for growth of Madin Darby Canine Kidney(MDCK)cells used in influenza vaccine production is described.Four classes of cells are considered:cells on microcarriers,cells in suspension,dead cells,and lysed cells.Based on experimental data,cell attachment and detachment is taken explicitly into account.The model allows simulation of the overall growth behavior in microcarrier culture,including the lag phase.In addition,it describes the time course of uptake and release of key metabolites and the identification of parameters relevant for the design and optimization of vaccine manufacturing processes.
机译：为了描述锚定依赖性哺乳动物细胞在微载体系统中的生长行为，过去已经提出了包括确定性和随机性单细胞模型以及基于自动机的模型在内的各种方法。这些受空间限制的经常接触抑制的细胞的生长限制相对于悬浮细胞系，这些细胞具有相对较长的滞后阶段，需要在微载体上进行附着和开始增殖。由于细胞生长空间的限制，培养基成分的限制以及生长抑制剂的积累，只能实现适度的指数生长。这里是Madin Darby犬肾（MDCK）细胞生长的基本确定性非结构化分离细胞模型描述了用于流感疫苗生产的四类细胞nsidered：微载体上的细胞，悬浮细胞，死细胞和裂解细胞。基于实验数据，明确考虑了细胞的附着和脱离。该模型可以模拟微载体培养中的总体生长行为，包括迟滞期。此外，它描述了关键代谢物的吸收和释放的时间过程，以及与疫苗生产过程的设计和优化有关的参数的确定。

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