Manufacturing mesenchymal stromal cells for the treatment of graft-versus-host disease: A survey amongst centers affiliated to the European Group of Blood and Marrow Transplantation

Cristina Trento, Maria Ester Bernardo, Arnon Nagler, Selim Kuçi, Martin Bornhäuser, Ulrike Köhl, Dirk Strunk, Antonio Galleu, Fermin Sanchez-Guijo, Giuseppe Gaipa, Martino Introna, Adomas Bukauskas, Katarina Le Blanc, Jane Apperley, Helene Roelofs, Ann Van Campenhout, Yves Beguin, Jürgen Kuball, Lorenza Lazzari, Maria Antonietta AvanziniWillem Fibbe, Christian Chabannon, Chiara Bonini, Francesco Dazzi

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    The immunosuppressive properties of mesenchymal stromal cells (MSC) have been successfully tested to control clinical severe graft-versus host disease (GvHD) and improve survival. However, clinical studies have not yet provided conclusive evidence of their efficacy largely because of lack of patients’ stratification criteria. The heterogeneity of MSC preparations is also a major contributing factor, as manufacturing of therapeutic MSC is performed according to different protocols amongst different centers. Understanding the variability of the manufacturing protocol would allow a better comparison of the results obtained in the clinical setting amongst different centers. In order to acquire information on MSC manufacturing we have sent a questionnaire to the European Group for Blood and Marrow Transplantation (EBMT) centers registered as producing MSC.

    Data from 17 centers were obtained and analyzed by means of a two-phase questionnaire specifically focused on product manufacturing. Gathered information included MSC tissue sources, MSC donor matching, medium additives for ex-vivo expansion, data on MSC product specification for clinical release.

    The majority of centers manufactured MSC from bone marrow (88%), whilst only two centers produced MSC from umbilical cord blood or cord tissue. One of the major changes in the manufacturing process has been the replacement of fetal bovine serum with human platelet lysate as medium supplement. 59% of centers used only third-party MSC, whilst only one center manufactured exclusively autologous MSC. The large majority (71%) of these facilities administered MSC exclusively from frozen batches. Aside from variations in the culture method, we found large heterogeneity also regarding product specification, particularly in the markers used for phenotypical characterization and their threshold of expression, use of potency assays to test MSC functionality and karyotyping.

    The initial data collected from this survey highlight the variability in MSC manufacturing as clinical products and the need for harmonization. Until more informative potency assays become available, a more homogeneous approach to cell production may at least reduce variability in clinical trials and improve interpretation of results.
    Original languageEnglish
    Early online date20 Jul 2018
    Publication statusPublished - 2018


    • Mesenchymal Stromal Cells
    • Graft-versus-Host Disease
    • cellular therapy
    • manufacturing
    • product specification
    • release criteria


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