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A quantitative approach for understanding small-scale human mesenchymal stem cell culture implications for large-scale bioprocess development

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journal contribution
posted on 23.06.2015 by Qasim Rafiq, Karen Coopman, Alvin W. Nienow, Christopher Hewitt
Human mesenchymal stem cell (hMSC) therapies have the potential to revolutionise the healthcare industry and replicate the success of the therapeutic protein industry; however, for this to be achieved there is a need to apply key bioprocessing engineering principles and adopt a quantitative approach for large-scale reproducible hMSC bioprocess development. Here we provide a quantitative analysis of the changes in concentration of glucose, lactate and ammonium with time during hMSC monolayer culture over 4 passages, under 100% and 20% dissolved oxgen (dO2), where either a 100%, 50% or 0% growth medium exchange was performed after 72h in culture. Yield coefficients, specific growth rates (h-1) and doubling times (h) were calculated for all cases. The 100% dO2 flasks outperformed the 20% dO2 flasks with respect to cumulative cell number, with the latter consuming more glucose and producing more lactate and ammonium. Furthermore, the 100% and 50% medium exchange conditions resulted in similar cumulative cell numbers, whilst the 0% conditions were significantly lower. Cell immunophenotype and multipotency were not affected by the experimental culture conditions. This study demonstrates the importance of determining optimal culture conditions for hMSC expansion and highlights a potential cost savings from only making a 50% medium exchange, which may prove significant for large-scale bioprocessing.

Funding

The authors would like to acknowledge the Biotechnology and Biological Sciences Research Council (BBSRC; UK) Bioprocessing Research Industries Club (BRIC), the Engineering and Physical Sciences Research Council (EPSRC; UK) and Lonza GmbH (Cologne, Germany) for their financial support.

History

School

  • Aeronautical, Automotive, Chemical and Materials Engineering

Department

  • Chemical Engineering

Published in

BIOTECHNOLOGY JOURNAL

Volume

8

Issue

4

Pages

459 - + (2)

Citation

RAFIQ, Q.A. ... et al, 2013. A quantitative approach for understanding small-scale human mesenchymal stem cell culture implications for large-scale bioprocess development. Biotechnology Journal, 8 (4), pp. 459 - 471

Publisher

© WILEY-VCH Verlag GmbH & Co.

Version

AM (Accepted Manuscript)

Publication date

2013

Notes

This is the peer reviewed version of the following article: RAFIQ, Q.A. ... et al, 2013. A quantitative approach for understanding small-scale human mesenchymal stem cell culture implications for large-scale bioprocess development. Biotechnology Journal, 8 (4), pp. 459 - 471, which has been published in final form at http://dx.doi.org/10.1002/biot.201200197. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.

ISSN

1860-6768

Language

en

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