Heathman et al_Agitation Aeration_for resubmision .pdf (1.15 MB)
Agitation and aeration of stirred-bioreactors for the microcarrier culture of human mesenchymal stem cells and potential implications for large-scale bioprocess development
journal contribution
posted on 2018-06-12, 10:14 authored by Thomas R.J. Heathman, Alvin W. Nienow, Qasim A. Rafiq, Karen CoopmanKaren Coopman, Bo Kara, Christopher J. HewittThe impact of agitation rate and sparged aeration on BM-hMSC expansion in conventional stirred tank bioreactors was assessed. It was found that a decrease in impeller speed to below N JS caused sampling difficulties, clumping and an increase to ∼2 N JS decreased the growth rate though an intermediate value of ∼1.3 N JS did not. Additionally, over this range of agitation intensities, cell quality remained unchanged post-harvest suggesting that poor growth performance at the highest speed was due to a failure of the cells to attach efficiently to microcarriers rather than damage to the cells due to fluid dynamic stress. Further it was shown that direct aeration of the culture medium both with and without Pluronic F68 via a sparger at N JS was detrimental to BM-hMSC growth. Again, this reduction in growth seems to be associated with poor attachment rather than cell damage, which due to the mechanism of Pluronic TM F68 reducing the cell hydrophobicity and thus the affinity of the BM-hMSCs to attach to the microcarrier, leads to a poorer performance in the presence of the surfactant. Certain post-harvest quality characteristics are also detrimentally impacted compared to headspace aeration. This problem is discussed in terms of the need to facilitate future large-scale process development where headspace aeration at N JS may not be sufficient to meet culture needs at higher cell densities.
Funding
This study has been funded by the Engineering and Physical Sciences Research Council (EPSRC) and FUJIFILM Diosynth Biotechnologies.
History
School
- Aeronautical, Automotive, Chemical and Materials Engineering
Department
- Chemical Engineering
Published in
Biochemical Engineering JournalVolume
136Pages
9 - 17Citation
HEATHMAN, T.R.J. ... et al, 2018. Agitation and aeration of stirred-bioreactors for the microcarrier culture of human mesenchymal stem cells and potential implications for large-scale bioprocess development. Biochemical Engineering Journal, 136, pp.9-17.Publisher
© ElsevierVersion
- 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
2018-04-16Publication date
2018Notes
This paper was accepted for publication in the journal Biochemical Engineering Journal and the definitive published version is available at https://doi.org/10.1016/j.bej.2018.04.011ISSN
1369-703XPublisher version
Language
- en