Optimisation of a Potency Assay for the Assessment of Immunomodulative Potential of Clinical Grade Multipotent Mesenchymal Stromal Cells

Overview

Journal Cytotechnology

Specialties Biotechnology
Genetics

Date 2018 Jan 12

PMID 29322348

Citations 14

Authors

Irene Oliver-Vila

Carmen Ramirez-Moncayo

Marta Grau-Vorster

Silvia Marin-Gallen

Marta Caminal

Joaquim Vives

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

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References

Codinach M, Blanco M, Ortega I, Lloret M, Reales L, Coca M . Design and validation of a consistent and reproducible manufacture process for the production of clinical-grade bone marrow-derived multipotent mesenchymal stromal cells. Cytotherapy. 2016; 18(9):1197-208. DOI: 10.1016/j.jcyt.2016.05.012. View

Schimke M, Marozin S, Lepperdinger G . Patient-Specific Age: The Other Side of the Coin in Advanced Mesenchymal Stem Cell Therapy. Front Physiol. 2015; 6:362. PMC: 4667069. DOI: 10.3389/fphys.2015.00362. View

Woods E, Thirumala S, Badhe-Buchanan S, Clarke D, Mathew A . Off the shelf cellular therapeutics: Factors to consider during cryopreservation and storage of human cells for clinical use. Cytotherapy. 2016; 18(6):697-711. DOI: 10.1016/j.jcyt.2016.03.295. View

Le Blanc K, Tammik C, Rosendahl K, Zetterberg E, Ringden O . HLA expression and immunologic properties of differentiated and undifferentiated mesenchymal stem cells. Exp Hematol. 2003; 31(10):890-6. DOI: 10.1016/s0301-472x(03)00110-3. View

Wang Y, Chen X, Cao W, Shi Y . Plasticity of mesenchymal stem cells in immunomodulation: pathological and therapeutic implications. Nat Immunol. 2014; 15(11):1009-16. DOI: 10.1038/ni.3002. View

Wagner W, Wein F, Seckinger A, Frankhauser M, Wirkner U, Krause U . Comparative characteristics of mesenchymal stem cells from human bone marrow, adipose tissue, and umbilical cord blood. Exp Hematol. 2005; 33(11):1402-16. DOI: 10.1016/j.exphem.2005.07.003. View

Reis M, Ogonek J, Qesari M, Borges N, Nicholson L, Preussner L . Recent Developments in Cellular Immunotherapy for HSCT-Associated Complications. Front Immunol. 2016; 7:500. PMC: 5107577. DOI: 10.3389/fimmu.2016.00500. View

Prockop D . The exciting prospects of new therapies with mesenchymal stromal cells. Cytotherapy. 2016; 19(1):1-8. PMC: 5154828. DOI: 10.1016/j.jcyt.2016.09.008. View

Vives J, Oliver-Vila I, Pla A . Quality compliance in the shift from cell transplantation to cell therapy in non-pharma environments. Cytotherapy. 2015; 17(8):1009-14. DOI: 10.1016/j.jcyt.2015.02.002. View

10.

Francois M, Copland I, Yuan S, Romieu-Mourez R, Waller E, Galipeau J . Cryopreserved mesenchymal stromal cells display impaired immunosuppressive properties as a result of heat-shock response and impaired interferon-γ licensing. Cytotherapy. 2011; 14(2):147-52. PMC: 3279133. DOI: 10.3109/14653249.2011.623691. View

11.

Schneider C, Salmikangas P, Jilma B, Flamion B, Todorova L, Paphitou A . Challenges with advanced therapy medicinal products and how to meet them. Nat Rev Drug Discov. 2010; 9(3):195-201. DOI: 10.1038/nrd3052. View

12.

Bocelli-Tyndall C, Zajac P, Di Maggio N, Trella E, Benvenuto F, Iezzi G . Fibroblast growth factor 2 and platelet-derived growth factor, but not platelet lysate, induce proliferation-dependent, functional class II major histocompatibility complex antigen in human mesenchymal stem cells. Arthritis Rheum. 2010; 62(12):3815-25. DOI: 10.1002/art.27736. View

13.

Quah B, Parish C . New and improved methods for measuring lymphocyte proliferation in vitro and in vivo using CFSE-like fluorescent dyes. J Immunol Methods. 2012; 379(1-2):1-14. DOI: 10.1016/j.jim.2012.02.012. View

14.

Bianco P, Cao X, Frenette P, Mao J, Robey P, Simmons P . The meaning, the sense and the significance: translating the science of mesenchymal stem cells into medicine. Nat Med. 2013; 19(1):35-42. PMC: 3998103. DOI: 10.1038/nm.3028. View

15.

Lyons A, Parish C . Determination of lymphocyte division by flow cytometry. J Immunol Methods. 1994; 171(1):131-7. DOI: 10.1016/0022-1759(94)90236-4. View

16.

Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D . Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 2006; 8(4):315-7. DOI: 10.1080/14653240600855905. View

17.

Nombela-Arrieta C, Ritz J, Silberstein L . The elusive nature and function of mesenchymal stem cells. Nat Rev Mol Cell Biol. 2011; 12(2):126-31. PMC: 3346289. DOI: 10.1038/nrm3049. View

18.

Guadix J, Zugaza J, Galvez-Martin P . Characteristics, applications and prospects of mesenchymal stem cells in cell therapy. Med Clin (Barc). 2017; 148(9):408-414. DOI: 10.1016/j.medcli.2016.11.033. View

19.

Bravery C, Carmen J, Fong T, Oprea W, Hoogendoorn K, Woda J . Potency assay development for cellular therapy products: an ISCT review of the requirements and experiences in the industry. Cytotherapy. 2012; 15(1):9-19. DOI: 10.1016/j.jcyt.2012.10.008. View

20.

Sensebe L, Bourin P, Tarte K . Good manufacturing practices production of mesenchymal stem/stromal cells. Hum Gene Ther. 2010; 22(1):19-26. DOI: 10.1089/hum.2010.197. View