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Systematic microcarrier screening and agitated culture conditions improves human mesenchymal stem cell yield in bioreactors

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posted on 2016-01-08, 11:52 authored by Qasim A. Rafiq, Karen CoopmanKaren Coopman, Alvin W. Nienow, Christopher J. Hewitt
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.

Funding

This paper was supported by the Engineering and Physical Sciences Research Council (EPSRC; UK) (EP/L015072/1).

History

School

  • Aeronautical, Automotive, Chemical and Materials Engineering

Department

  • Chemical Engineering

Published in

Biotechnology Journal

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.

Publisher

© 2015 The Authors. Biotechnology Journal published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Version

  • VoR (Version of Record)

Publisher statement

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: https://creativecommons.org/licenses/by/4.0/

Publication date

2016

Notes

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.

ISSN

1860-7314

Language

  • en

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