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Model-based analysis and optimization of bioreactor for hematopoietic stem cell cultivation

机译：基于模型的造血干细胞生物反应器分析与优化

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摘要

One of the problems to be solved in attaining the full potentials of hematopoietic stem cell (HSC) applications is the limited availability of the cells. Growing HSCs in a bioreactor offers an alternative solution to this problem. Besides, it also offers the advantages of eliminating labour intensive process as well as the possible contamination involved in the periodic nutrient replenishments in the traditional T-flask stem cell cultivation. In spite of this, the optimization of HSC cultivation in a bioreactor has been barely explored. This manuscript discusses the development of a mathematical model to describe the dynamics in nutrient distribution and cell concentration of an ex vivo HSC cultivation in a micro-channel perfusion bioreactor. The model was further used to optimize the cultivation by proposing three alternative feeding strategies in order to prevent the occurrence of nutrient limitation in the bioreactor. The evaluation of these strategies, the periodic step change increase in the inlet oxygen concentration, the periodic step changernincrease in the media inflow, and the feedback control of media inflow, shows that these strategies can successfully improve the cell yield of the bioreactor. In general, the developed model is useful for the design and optimization of bioreactor operation.
机译：在获得造血干细胞（HSC）应用的全部潜力方面要解决的问题之一是细胞的有限可用性。在生物反应器中生长HSC提供了解决此问题的替代解决方案。此外，它还具有消除劳动密集型过程的优点，以及在传统的T瓶干细胞培养中定期补充营养元素可能带来的污染。尽管如此，几乎没有探索在生物反应器中HSC培养的优化。该手稿讨论了数学模型的发展，该数学模型描述了微通道灌注生物反应器中离体HSC培养物中营养物质分布和细胞浓度的动态变化。为了防止生物反应器中养分限制的发生，该模型还通过提出三种替代的饲喂策略来优化培养。对这些策略的评估，入口氧浓度的周期性变化，介质流入的周期性变化增加以及介质流入的反馈控制表明，这些策略可以成功地提高生物反应器的细胞产量。通常，开发的模型可用于设计和优化生物反应器的操作。

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  • 来源
    《Bioprocess and Biosystems Engineering》 |2011年第1期|p.81-93|共13页
  • 作者

    M. T. A. P. Kresnowati; rnG. M. Forde; rnX. D. Chen;

  • 作者单位

    Bioprocess and Microbiology Laboratory,Department of Chemical Engineering,Faculty of Industrial Technology,Bandung Institute of Technology,Ganesha 10, Bandung 40132, Indonesia Bio Engineering Laboratory (BEL),Department of Chemical Engineering, Monash University,Clayton, VIC 3800, Australia;

    rnBio Engineering Laboratory (BEL),Department of Chemical Engineering, Monash University,Clayton, VIC 3800, Australia;

    rnBiotechnology and Food Engineering Group,Department of Chemical Engineering, Monash University,Clayton, VIC 3800, Australia;

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  • 正文语种 eng
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  • 关键词

    modelling; optimization; feeding strategy; bioreactor; hematopoietic stem cell;

    机译：造型;优化;喂养策略;生物反应器造血干细胞;

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