Closed system isolation and scalable expansion of human placental mesenchymal stem cells

Authors

  • N.E. Timmins,

    Corresponding author
    1. Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St Lucia, QLD 4072, Australia, telephone: +61-7-3346-4219; fax: +61-7-3346-3973
    • Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St Lucia, QLD 4072, Australia, telephone: +61-7-3346-4219; fax: +61-7-3346-3973.
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  • M. Kiel,

    1. Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St Lucia, QLD 4072, Australia, telephone: +61-7-3346-4219; fax: +61-7-3346-3973
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  • M. Günther,

    1. Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St Lucia, QLD 4072, Australia, telephone: +61-7-3346-4219; fax: +61-7-3346-3973
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  • C. Heazlewood,

    1. Adult Stem Cell Laboratory, Biotherapy Program, Mater Medical Research Institute, Aubigny Place, Raymond Tce, South Brisbane, QLD, Australia
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  • M.R. Doran,

    1. Stem Cell Therapies Laboratory, Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, QLD, Australia
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  • G. Brooke,

    1. Adult Stem Cell Laboratory, Biotherapy Program, Mater Medical Research Institute, Aubigny Place, Raymond Tce, South Brisbane, QLD, Australia
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  • K. Atkinson

    1. Adult Stem Cell Laboratory, Biotherapy Program, Mater Medical Research Institute, Aubigny Place, Raymond Tce, South Brisbane, QLD, Australia
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Abstract

Mesenchymal stem cells (MSC) are emerging as a leading cellular therapy for a number of diseases. However, for such treatments to become available as a routine therapeutic option, efficient and cost-effective means for industrial manufacture of MSC are required. At present, clinical grade MSC are manufactured through a process of manual cell culture in specialized cGMP facilities. This process is open, extremely labor intensive, costly, and impractical for anything more than a small number of patients. While it has been shown that MSC can be cultivated in stirred bioreactor systems using microcarriers, providing a route to process scale-up, the degree of numerical expansion achieved has generally been limited. Furthermore, little attention has been given to the issue of primary cell isolation from complex tissues such as placenta. In this article we describe the initial development of a closed process for bulk isolation of MSC from human placenta, and subsequent cultivation on microcarriers in scalable single-use bioreactor systems. Based on our initial data, we estimate that a single placenta may be sufficient to produce over 7,000 doses of therapeutic MSC using a large-scale process. Biotechnol. Bioeng. 2012; 109:1817–1826. © 2012 Wiley Periodicals, Inc.

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