Manufacturing Mesenchymal Stromal Cells for the Treatment of Graft-versus-Host Disease: A Survey among Centers Affiliated with the European Society for Blood and Marrow Transplantation

Trento, C.; Bernardo, M. E.; Nagler, A.; Kuçi, S.; Bornhäuser, M.; Köhl, U.; Strunk, D.; Galleu, A.; Sanchez-Guijo, F.; Gaipa, G.; Introna, M.; Bukauskas, A.; Le Blanc, K.; Apperley, J.; Roelofs, H.; Van Campenhout, A.; Beguin, Yves; Kuball, J.; Lazzari, L.; Avanzini, M. A.; Fibbe, W.; Chabannon, C.; Bonini, C.; Dazzi, F.

doi:10.1016/j.bbmt.2018.07.015

Article (Scientific journals)

Manufacturing Mesenchymal Stromal Cells for the Treatment of Graft-versus-Host Disease: A Survey among Centers Affiliated with the European Society for Blood and Marrow Transplantation

Trento, C.; Bernardo, M. E.; Nagler, A. et al.

2018 • In Biology of Blood and Marrow Transplantation, 24, p. 2365-2370

Peer Reviewed verified by ORBi

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https://hdl.handle.net/2268/232301

DOI
10.1016/j.bbmt.2018.07.015

PubMed
30031938

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Keywords :

Cellular therapy; Graft-versus-host disease; Manufacturing; Mesenchymal stromal cells; Product specification; Release criteria

Abstract :

[en] The immunosuppressive properties of mesenchymal stromal cells (MSC) have been successfully tested to control clinical severe graft-versus host disease 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 among different centers. Understanding the variability of the manufacturing protocol would allow a better comparison of the results obtained in the clinical setting among different centers. In order to acquire information on MSC manufacturing we sent a questionnaire to the European Society for Blood and Marrow Transplantation centers registered as producing MSC. Data from 17 centers were obtained and analyzed by means of a 2-phase questionnaire specifically focused on product manufacturing. Gathered information included MSC tissue sources, MSC donor matching, medium additives for ex vivo expansion, and data on MSC product specification for clinical release. The majority of centers manufactured MSC from bone marrow (88%), whilst only 2 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 1 center manufactured exclusively autologous MSC. The large majority of these facilities (71%) 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. © 2018

Disciplines :

Hematology

Author, co-author :

Trento, C.; School of Cancer & Pharmaceutical Sciences, King's College London, London, United Kingdom, United Kingdom

Bernardo, M. E.; Pediatric Immunohematology and Bone Marrow Transplantation Unit, San Raffaele Telethon Institute for Gene Therapy (TIGET), San Raffaele Scientific Institute, Milan, Italy, Italy

Nagler, A.; Hematology Division, Chaim Sheba Medical Center, Tel Aviv University, Tel-Hashomer, Israel

Kuçi, S.; Division for Stem Cell Transplantation and Immunology, Frankfurt am Main, Germany

Bornhäuser, M.; Medizinische Klinik und Poliklinik I, Dresden, Germany

Köhl, U.; Institute of Clinical Immunology, University Leipzig, Leipzig, Germany, Fraunhofer Institute of Cellular Therapy and Immunology and Institute of Cellular Therapeutics, Hannover Medical School, Hannover, Germany

Strunk, D.; Experimental & Clinical Cell Therapy Institute, Spinal Cord Injury and Tissue Regeneration Center, Paracelsus Medical University, Salzburg, Austria

Galleu, A.; School of Cancer & Pharmaceutical Sciences, King's College London, London, United Kingdom, United Kingdom

Sanchez-Guijo, F.; Hematology Department, IBSAL-Hospital Universitario de Salamanca, University of Salamanca, Salamanca, Spain

Gaipa, G.; Laboratorio di Terapia Cellulare e Genica Stefano Verri, ASST Monza, Monza, Italy

More authors (14 more)

Language :

English

Title :

Manufacturing Mesenchymal Stromal Cells for the Treatment of Graft-versus-Host Disease: A Survey among Centers Affiliated with the European Society for Blood and Marrow Transplantation

Publication date :

2018

Journal title :

Biology of Blood and Marrow Transplantation

ISSN :

1083-8791

eISSN :

1523-6536

Publisher :

Elsevier Inc.

Volume :

Pages :

2365-2370

Peer reviewed :

Peer Reviewed verified by ORBi

Funders :

AIRC - Associazione Italiana per la Ricerca sul Cancro [IT]
GSK - GlaxoSmithKline [BE]

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since 29 January 2019

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