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Mesenchymal stromal cell therapy: progress in manufacturing and assessments of potency

  • KEVIN P. ROBB
    Affiliations
    The Arthritis Program, University Health Network, Toronto, Canada;

    Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Canada
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  • JOAN C. FITZGERALD
    Affiliations
    Regenerative Medicine Institute (REMEDI), National University of Ireland, Galway, Ireland
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  • FRANK BARRY
    Affiliations
    The Arthritis Program, University Health Network, Toronto, Canada;

    Regenerative Medicine Institute (REMEDI), National University of Ireland, Galway, Ireland
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  • SOWMYA VISWANATHAN
    Correspondence
    Correspondence: Sowmya Viswanathan, PhD; Assistant Professor, Institute of Biomaterials and Biomedical Engineering, University of Toronto; Affiliate Scientist, Krembil Research Institute, University Health Network. Krembil Research Institute, 60 Leonard Avenue, Rm 3KD479, Toronto, Ontario, M5T 2S8.
    Affiliations
    The Arthritis Program, University Health Network, Toronto, Canada;

    Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Canada

    Cell Therapy Program, University Health Network, Toronto, Canada

    Division of Hematology, Department of Medicine, University of Toronto, Toronto, Canada
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Published:December 06, 2018DOI:https://doi.org/10.1016/j.jcyt.2018.10.014

      Abstract

      Mesenchymal stromal cell (MSC) therapies have been pursued for a broad spectrum of indications but mixed reports on clinical efficacy have given rise to some degree of skepticism regarding the effectiveness of this approach. However, recent reports of successful clinical outcomes and regulatory approvals for graft-versus-host disease, Crohn's disease and critical limb ischemia have prompted a shift in this perspective. With hundreds of clinical trials involving MSCs currently underway and an increasing demand for large-scale manufacturing protocols, there is a critical need to develop standards that can be applied to processing methods and to establish consensus assays for both MSC processing control and MSC product release. Reference materials and validated, uniformly applied tests for quality control of MSC products are needed. Here, we review recent developments in MSC manufacturing technologies, release testing and potency assays. We conclude that, although MSCs hold considerable promise clinically, economies of scale have yet to be achieved although numerous bioreactor technologies for scalable production of MSCs exist. Additionally, rigorous disease-specific product testing and comprehensive understanding of mechanisms of action, which are linked to relevant process and product release potency assays, will be required to ensure that these therapies continue to be successful.

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