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Mixing theory for culture and harvest in bioreactors of human mesenchymal stem cells on microcarriers

Theoretical Foundations of Chemical Engineering volume 50, pages 895–900 (2016)Cite this article

Abstract

The use of human mesenchymal stem cells (hMSCs) in regenerative medicine is a potential major advance for the treatment of many medical conditions, especially with the use of allogeneic therapies where the cells from a single donor can be used to treat ailments in many patients. Such cells must be grown attached to surfaces and for large scale production, it is shown that stirred bioreactors containing ~200 μm particles (microcarriers) can provide such a surface. It is also shown that the just suspended condition, agitator speed N JS, provides a satisfactory condition for cell growth by minimizing the specific energy dissipation rate, εT, in the bioreactor whilst still meeting the oxygen demand of the cells. For the cells to be used for therapeutic purposes, they must be detached from the microcarriers before being cryopreserved. A strategy based on a short period (~7 min) of very high εT, based on theories of secondary nucleation, is effective at removing >99% cells. Once removed, the cells are smaller than the Kolmogorov scale of turbulence and hence not damaged. This approach is shown to be successful for culture and detachment in 4 types of stirred bioreactors from 15 mL to 5 L.

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Authors and Affiliations

  1. School of Chemical Engineering, University of Birmingham, Birmingham, B15 2TT, UK

    A. W. Nienow

  2. Centre for Biological Engineering, Loughborough University, Loughborough, LE11 3TU, UK

    A. W. Nienow, Q. A. Rafiq, T. R. J. Heathman, K. Coopman & C. J. Hewitt

  3. Aston Medical Research Institute, School of Life and Health Sciences, Aston University, Birmingham, B4 7ET, UK

    Q. A. Rafiq & C. J. Hewitt

Authors
  1. A. W. Nienow
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  2. Q. A. Rafiq
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  3. T. R. J. Heathman
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  4. K. Coopman
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  5. C. J. Hewitt
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Correspondence to A. W. Nienow.

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Nienow, A.W., Rafiq, Q.A., Heathman, T.R.J. et al. Mixing theory for culture and harvest in bioreactors of human mesenchymal stem cells on microcarriers. Theor Found Chem Eng 50, 895–900 (2016). https://doi.org/10.1134/S0040579516060117

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  • DOI: https://doi.org/10.1134/S0040579516060117

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