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Serum-free process development: improving the yield and consistency of human mesenchymal stem cell production

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posted on 2015-10-02, 11:45 authored by Thomas Heathman, Alexandra StolzingAlexandra Stolzing, Claire Fabian, Qasim A. Rafiq, Alvin W. Nienow, Karen CoopmanKaren Coopman, Bo Kara, Christopher J. Hewitt
Background: The cost effective production of hMSCs for off-the-shelf and patient specific therapies will require an increasing focus on improving product yield and driving manufacturing consistency. Methods: Bone-marrow derived hMSCs from two donors were expanded for 36 days in monolayer with medium supplemented with either fetal bovine serum (FBS) or PRIME-XV® Serum-free Medium (SFM). Cells were assessed throughout culture for proliferation, mean cell diameter, colony forming potential, osteogenic potential, gene expression and metabolites. Results: Expansion of BM-hMSCs in PRIME-XV® SFM resulted in a significantly higher growth rate (p < 0.001) and increased consistency between donors compared with FBS-based culture. FBS-based culture showed an inter batch production range of 0.9 and 5 days per dose compared with 0.5 and 0.6 days in SFM for each BM-hMSC donor line. The consistency between donors was also improved by the use of PRIME-XV® SFM, with a production range of 0.9 days compared with 19.4 days in FBS-based culture. Mean cell diameter has also been demonstrated as a process metric for BM-hMSC growth rate and senescence via a correlation (R2 = 0.8705) across all conditions. PRIME-XV® SFM has also shown increased consistency in BM-hMSC characteristics such as per cell metabolite utilisation, in vitro colony forming potential and osteogenic potential despite the higher number of population doublings. Conclusions: We have increased the yield and consistency of BM-hMSC expansion between donors, demonstrating a level of control over the product, which has the potential to increase the cost effectiveness and reduce the risk in these manufacturing processes.

Funding

This study has been funded by the Engineering and Physical Sciences Research Council (EPSRC) and FUJIFILM Diosynth Biotechnologies.

History

School

  • Mechanical, Electrical and Manufacturing Engineering

Published in

Cytotherapy

Citation

HEATHMAN, T.R.J. ...et al., 2015. Serum-free process development: improving the yield and consistency of human mesenchymal stem cell production. Cytotherapy, 17(11), pp.1524-1535.

Publisher

© Elsevier

Version

  • NA (Not Applicable or Unknown)

Publisher statement

This work is made available according to the conditions of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC-BY 4.0) licence. Full details of this licence are available at: https://creativecommons.org/licenses/by/4.0/

Publication date

2015

Notes

This is an Open Access Article. It is published by Elsevier under the Creative Commons Attribution 4.0 Unported Licence (CC BY). Full details of this licence are available at: http://creativecommons.org/licenses/by/4.0/

ISSN

1477-2566

Language

  • en