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Title: Mixing theory for culture and harvest in bioreactors of human mesenchymal stem cells on microcarriers
Authors: Nienow, Alvin W.
Rafiq, Qasim A.
Heathman, Thomas R.J.
Coopman, Karen
Hewitt, Christopher J.
Keywords: Mesenchymal stem cells
Issue Date: 2016
Publisher: Springer © Pleiades Publishing
Citation: NIENOW, A.W. ... et al, 2016. Mixing theory for culture and harvest in bioreactors of human mesenchymal stem cells on microcarriers. Theoretical Foundations of Chemical Engineering, 50 (6), pp. 895-900.
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 NJS, 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.
Description: This paper was accepted for publication in the journal Theoretical Foundations of Chemical Engineering and the definitive published version is available at http://dx.doi.org/10.1134/S0040579516060117.
Sponsor: The authors would like to acknowledge the UK Engineering and Physical Sciences Research Council (EPSRC), Lonza Cologne AG and FujiFilm Diosynth Biotechnologies for funding.
Version: Accepted for publication
DOI: 10.1134/S0040579516060117
URI: https://dspace.lboro.ac.uk/2134/25736
Publisher Link: http://dx.doi.org/10.1134/S0040579516060117
ISSN: 0040-5795
Appears in Collections:Published Articles (Chemical Engineering)

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