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

Kresnowati, M.T.A.P., Forde, G.M., & Chen, X.D. (2011) Model-based analysis and optimization of bioreactor for hematopoietic stem cell cultivation. Bioprocess and Biosystems Engineering, 34(1), pp. 81-93.

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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 microchannel 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 change increase 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.

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ID Code: 81526
Item Type: Journal Article
Refereed: Yes
Keywords: Bioreactor, Feeding strategy, Hematopoietic stem cell, Modelling, Optimization, Cell concentrations, Cell yields, Design and optimization, Developed model, Ex-vivo, Feeding strategies, Hematopoietic stem cells, Labour-intensive, Model-based analysis, Nutrient distributions, Nutrient limitations, Oxygen concentrations, Perfusion bioreactor, Stem cell, Step changes, Bioconversion, Bioreactors, Cultivation, Feeding, Mathematical models, Nutrients, Oxygen, Stem cells, article, bioreactor design, cell culture, cell growth, cell heterogeneity, cell hypoxia, cell metabolism, cell population, controlled study, culture medium, ex vivo study, fed batch culture, growth rate, mathematical model, Michaelis Menten kinetics, molecular dynamics, nutrient concentration, nutrient limitation, nutrient uptake, oxygen concentration, oxygen saturation, priority journal, process development, process model, reactor monitoring, reactor operation, reactor optimization, validation process, Algorithms, Animals, Cell Culture Techniques, Cells, Cultured, Computer Simulation, Humans, Models, Theoretical, Perfusion
DOI: 10.1007/s00449-010-0449-z
ISSN: 1615-7591
Divisions: Current > Schools > School of Chemistry, Physics & Mechanical Engineering
Current > QUT Faculties and Divisions > Science & Engineering Faculty
Deposited On: 05 Feb 2015 23:51
Last Modified: 11 Feb 2015 01:10

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