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Agitation and aeration of stirred-bioreactors for the microcarrier culture of human mesenchymal stem cells and potential implications for large-scale bioprocess development

Heathman, TRJ; Nienow, AW; Rafiq, QA; Coopman, K; Kara, B; Hewitt, CJ; (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. 10.1016/j.bej.2018.04.011. Green open access

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Abstract

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 NJScaused sampling difficulties, clumping and an increase to ∼2 NJSdecreased the growth rate though an intermediate value of ∼1.3 NJSdid 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 NJSwas 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 PluronicTMF68 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 NJSmay not be sufficient to meet culture needs at higher cell densities.

Type: Article
Title: Agitation and aeration of stirred-bioreactors for the microcarrier culture of human mesenchymal stem cells and potential implications for large-scale bioprocess development
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.bej.2018.04.011
Publisher version: https://doi.org/10.1016/j.bej.2018.04.011
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Process control, Human mesenchymal stem cell, Microcarrier expansion,Harvest, Agitation, Aeration
UCL classification: UCL
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Biochemical Engineering
URI: https://discovery.ucl.ac.uk/id/eprint/10051201
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