Optimisation of a potency assay for the assessment of immunomodulative potential of clinical grade multipotent mesenchymal stromal cells
Clinical use of multipotent Mesenchymal Stromal Cell (MSC)-based medicinal products requires their production in compliance with Good Manufacturing Practices, thus ensuring that the final drug product meets specifications consistently from batch to batch in terms of cell viability, identity, purity and potency. Potency relates to the efficacy of the medicine in its target clinical indication, so adequate release tests need to be defined and validated as quality controls. Herein we report the design and optimisation of parameters affecting the performance of an in vitro cell-based assay for assessing immunomodulatory potential of clinical grade MSC for human use, based on their capacity to inhibit proliferation of T lymphocytes under strong polyclonal stimuli. The resulting method was demonstrated to be reproducible and relatively simple to execute. Two case studies using clinical grade MSC are presented as examples to illustrate the applicability of the methodology described in this work.
KeywordsMultipotent Mesenchymal Stromal Cell Immunomodulative potential Potency assay Cellular therapy Cell culture Lymphocyte Cell-based assay Co-culture
The authors would like to acknowledge J. García-López, A. Pla, J. A. Marco, for technical support and advice; E. Valdivia and N. Martínez, for supplying blood samples; and M. Blanco and M. Codinach, for supplying MSC. We also want to thank Dr. Sergi Querol for critical review of the manuscript. This work was supported by “Fundació la Marató de TV3” (expedient No. 122831) and the Spanish Cell Therapy Network (TerCel, expedient No. RD16/0011/0028); and developed in the context of AdvanceCat with the support of ACCIÓ (Catalonia Trade & Investment; Generalitat de Catalunya) under the Catalonian ERDF operational program (European Regional Development Fund) 2014–2020. Figure 1 has been produced using Servier Medical Art (http://smart.servier.com).
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