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Title: Systematic microcarrier screening and agitated culture conditions improves human mesenchymal stem cell yield in bioreactors
Authors: Rafiq, Qasim A.
Coopman, Karen
Nienow, Alvin W.
Hewitt, Christopher J.
Keywords: Human mesenchymal stem cell
Cell therapy bioprocessing
Regenerative medicine
Issue Date: 2016
Publisher: © 2015 The Authors. Biotechnology Journal published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Citation: RAFIQ, Q.A. ...et al., 2016. Systematic microcarrier screening and agitated culture conditions improves human mesenchymal stem cell yield in bioreactors. Biotechnology Journal, 11 (4), pp. 473–486.
Abstract: Production of human mesenchymal stem cells for allogeneic cell therapies requires scalable, cost-effective manufacturing processes. Microcarriers enable the culture of anchorage-dependent cells in stirred-tank bioreactors. However, no robust, transferable methodology for microcarrier selection exists, with studies providing little or no reason explaining why a microcarrier was employed. We systematically evaluated 13 microcarriers for human bone marrow-derived MSC (hBM-MSCs) expansion from three donors to establish a reproducible and transferable methodology for microcarrier selection. Monolayer studies demonstrated input cell line variability with respect to growth kinetics and metabolite flux. HBM-MSC1 underwent more cumulative population doublings over three passages in comparison to hBM-MSC2 and hBM-MSC3. In 100 mL spinner flasks, agitated conditions were significantly better than static conditions, irrespective of donor, and relative microcarrier performance was identical where the same microcarriers outperformed others with respect to growth kinetics and metabolite flux. Relative growth kinetics between donor cells on the microcarriers were the same as the monolayer study. Plastic microcarriers were selected as the optimal microcarrier for hBM-MSC expansion. HBM-MSCs were successfully harvested and characterised, demonstrating hBM-MSC immunophenotype and differentiation capacity. This approach provides a systematic method for microcarrier selection, and the findings identify potentially significant bioprocessing implications for microcarrier-based allogeneic cell therapy manufacture.
Description: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Sponsor: This paper was supported by the Engineering and Physical Sciences Research Council (EPSRC; UK) (EP/L015072/1).
Version: Published
DOI: 10.1002/biot.201400862
URI: https://dspace.lboro.ac.uk/2134/19978
Publisher Link: http://dx.doi.org/10.1002/biot.201400862
ISSN: 1860-7314
Appears in Collections:Published Articles (Chemical Engineering)

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