Loughborough University
Browse
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

Download (1.15 MB)
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. Hewitt
The 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 Journal

Volume

136

Pages

9 - 17

Citation

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

© Elsevier

Version

  • 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

2018-04-16

Publication date

2018

Notes

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.2018.04.011

ISSN

1369-703X

Language

  • en

Usage metrics

    Loughborough Publications

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC