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Scalability and process transfer of mesenchymal stromal cell production from monolayer to microcarrier culture using human platelet lysate

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posted on 04.02.2016, 13:35 by Thomas Heathman, Alexandra StolzingAlexandra Stolzing, Claire Fabian, Qasim A. Rafiq, Karen CoopmanKaren Coopman, Alvin W. Nienow, Bo Kara, Christopher J. Hewitt
Background: The selection of medium and associated reagents for human mesenchymal stromal cell (hMSC) culture forms an integral part of manufacturing process development and must be suitable for multiple process scales and expansion technologies. Methods: In this work, we have expanded BM-hMSCs in fetal bovine serum (FBS)- and human platelet lysate (HPL)-containing media in both a monolayer and a suspension-based microcarrier process. Results: The introduction of HPL into the monolayer process increased the BM-hMSC growth rate at the first experimental passage by 0.049 day-1 and 0.127 day-1 for the two BM-hMSC donors compared to the FBS-based monolayer process. This increase in growth rate in HPLcontaining medium was associated with an increase in the inter-donor consistency, with an inter-donor range of 0.406 cumulative population doublings after 18 days compared with 2.013 in FBS-containing medium. Identity and quality characteristics of the BM-hMSCs are also comparable between conditions, in terms of colony-forming potential, osteogenic potential and expression of key genes during monolayer and post-harvest from microcarrier expansion. BMhMSCs cultured on microcarriers in HPL-containing medium demonstrated a reduction in the initial lag phase for both BM-hMSC donors and an increased BM-hMSC yield following six days of culture to 1.20 ± 0.17 x 105 and 1.02 ± 0.005 x 105 cells .mL-1 compared with 0.79 ± 0.05 x 105 and 0.36 ± 0.04 x 105 cells .mL-1 in FBS-containing medium. Conclusions: This study has demonstrated that HPL, in comparison with FBS-containing medium, delivers increased growth and comparability across two BM-hMSC donors between monolayer and microcarrier culture, which will have key implications for process transfer during scale-up.


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



  • Aeronautical, Automotive, Chemical and Materials Engineering


  • Chemical Engineering

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HEATHMAN, T.R.J. ... et al., 2016. Scalability and process transfer of mesenchymal stromal cell production from monolayer to microcarrier culture using human platelet lysate. Cytotherapy, 18(4), pp.523-535.




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

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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/