Mixing Theory for Culture and Harvest in Bioreactors of Human Mesenchymal Stem Cells on Microcarriers3.pdf (390.18 kB)
Mixing theory for culture and harvest in bioreactors of human mesenchymal stem cells on microcarriers
journal contribution
posted on 2017-07-07, 13:31 authored by Alvin W. Nienow, Qasim A. Rafiq, Thomas R.J. Heathman, Karen CoopmanKaren Coopman, Christopher J. HewittThe 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.
Funding
The authors would like to acknowledge the UK Engineering and Physical Sciences Research Council (EPSRC), Lonza Cologne AG and FujiFilm Diosynth Biotechnologies for funding.
History
School
- Aeronautical, Automotive, Chemical and Materials Engineering
Department
- Chemical Engineering
Published in
Theoretical Foundations of Chemical EngineeringVolume
50Issue
6Pages
895 - 900Citation
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.Publisher
Springer © Pleiades PublishingVersion
- AM (Accepted Manuscript)
Publisher statement
This work is made available according to the conditions of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) licence. Full details of this licence are available at: https://creativecommons.org/licenses/by-nc-nd/4.0/Acceptance date
2016-09-02Publication date
2016-12-02Copyright date
2016Notes
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.ISSN
0040-5795eISSN
1608-3431Publisher version
Language
- en