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


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.

Publication DOI: https://doi.org/10.1134/S0040579516060117
Divisions: College of Health & Life Sciences
Additional Information: The final publication is available at Springer via http://dx.doi.org/10.1134/S0040579516060117 Proceedings of XXV European Conference on Mixing “MIXING 15” Funding: EPSRC, Lonza Cologne AG and FujiFilm Diosynth Biotechnologies.
Uncontrolled Keywords: bioreactors,detachment,growth,mesenchymal stem cells,microcarriers,suspension,Chemistry(all),Chemical Engineering(all)
Publication ISSN: 0040-5795
Last Modified: 29 Feb 2024 08:13
Date Deposited: 19 Dec 2016 15:45
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Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
http://link.spr ... 040579516060117 (Publisher URL)
PURE Output Type: Article
Published Date: 2016-12-02
Accepted Date: 2016-10-20
Submitted Date: 2015-08-06
Authors: Nienow, A.W.
Rafiq, Q.A.
Heathman, T.R.J.
Coopman, K.
Hewitt, C.J. (ORCID Profile 0000-0001-6988-6071)



Version: Accepted Version

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