Use of Flow Cytometry for Quality Evaluation of Biomedical Cell Products
https://doi.org/10.30895/2221-996X-2018-18-1-16-24
Abstract
Flow cytometry is the most common method of identification and quantitation of cell surface markers. Flow cytometry can be used for cell counting and characterization of cell types and subtypes by labeling cells with fluorochrome-conjugated monoclonal antibodies. Manufacturers of human cell-based medicinal products have accumulated significant experience in flow cytometry and developed a large number of procedures that can be validated and included into cell products specifications. The present review summarises the experience gained with the use of flow cytometry for characterization of human cell lines used to develop cell therapy products. Since all biomedical cell products (BMCPs) have a cellular component, it will be necessary to use the flow cytometry method for identification testing of BMCPs during evaluation of their quality.
About the Authors
G. A. Trusov
Federal State Budgetary Institution «Scientific Centre for Expert Evaluation of Medicinal Products» of the Ministry of Health of the Russian Federation
Russian Federation
Russian Federation
2nd Professional Category Expert of the Laboratory of Biomedical Cell Products of the Testing Centre for Evaluation of Medicinal Products’ Quality
8/2 Petrovsky boulevard, Moscow 127051, Russian Federation
A. A. Chaplenko
Federal State Budgetary Institution «Scientific Centre for Expert Evaluation of Medicinal Products» of the Ministry of Health of the Russian Federation
Russian Federation
Russian Federation
2nd Professional Category Expert of the Laboratory of Biomedical Cell Products of the Testing Centre for Evaluation of Medicinal Products’ Quality
8/2 Petrovsky boulevard, Moscow 127051, Russian Federation
I. S. Semenova
Federal State Budgetary Institution «Scientific Centre for Expert Evaluation of Medicinal Products» of the Ministry of Health of the Russian Federation
Russian Federation
Russian Federation
1st Professional Category Expert of the Laboratory of Biomedical Cell Products of the Testing Centre for Evaluation of Medicinal Products’ Quality. Candidate of Biological Sciences
8/2 Petrovsky boulevard, Moscow 127051, Russian Federation
E. V. Melnikova
Federal State Budgetary Institution «Scientific Centre for Expert Evaluation of Medicinal Products» of the Ministry of Health of the Russian Federation
Russian Federation
Russian Federation
Leading Expert of the Laboratory of Biomedical Cell Products of the Testing Centre for Evaluation of Medicinal Products’ Quality. Candidate of Biological Sciences
8/2 Petrovsky boulevard, Moscow 127051, Russian Federation
Yu. V. Olefir
Federal State Budgetary Institution «Scientific Centre for Expert Evaluation of Medicinal Products» of the Ministry of Health of the Russian Federation
Russian Federation
Russian Federation
General Director. Doctor of Medical Sciences
8/2 Petrovsky boulevard, Moscow 127051, Russian Federation
References
1. United States Pharmacopeia: United States Pharmacopeial Convention. 37th ed.
2. European Pharmacopoeia: EDQM. 8th ed. Available from: http://online.edqm.eu/entry.htm
3. Carmen J, Burger SR, McCaman M, Rowley JA. Developing Assays to address Identity, Potency, Purity and Safety: Cell Characterization in Cell Therapy Process Development. Regen Med. 2012; 7(1): 85–100.
4. Commission Directive 2009/120/EC of 14 September 2009 Amending Directive 2001/83/EC of the European Parliament and of the Council on the Community Code Relating to Medicinal Products for Human Use as Regards Advanced Therapy Medicinal Products. Available from: https://ec.europa.eu/health/sites/health/files/files/eudralex/vol- 1/dir_2009_120/dir_2009_120_en.pdf
5. ICH Q6B Note for Guidance on Specifications: Test Procedures and Acceptance Criteria for Biotechnological/Biological Products (CPMP/ICH/365/96). Available from: http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500002824.pdf
6. Guideline on Human Cell-based Medicinal Products (EMEA/CHMP/410869/2006). Available from: http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003894.pdf
7. Bravery CA, Carmen J, Fong T, Oprea W, Hoogendoorn KH, Woda J, et al. Potency Assay Development for Cellular Therapy Products: an ISCT Review of the Requirements and Experiences in the Industry. Cytotherapy 2013; 15(1): 9–19.
8. SME Workshop on CMC of Biological Medicinal Products. EMA London 14–16.04.2015. CMC ISSUES for Cell Based ATMP. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/Presentation/2015/05/WC500187353.pdf
9. Order of Ministry of Health of the Russian Federation No. 14n of January 19, 2017 (In Russ.)
10. Donnenberg VS, Ulrich H, Tárnok A. Cytometry in Stem Cell Research and Therapy. Cytometry A. 2013; 83(1): 1–4.
11. Aghaeepour N, Finak G, Hoos H, Mosmann TR, Brinkman R, et al. Critical Assessment of Automated Flow Cytometry Data Analysis Techniques. Nat Methods 2013; 10: 228–38.
12. Maecker HT, McCoy JP, Nussenblatt R. Standardizing Immunophenotyping for the Human Immunology Project. Nat Rev Immunol. 2012; 12(3): 191–200.
13. O’Neill K, Aghaeepour N, Špidlen J, Brinkman R. Flow Cytometry Bioinformatics. PLoS Comput Biol. 2013; 9(12): e1003365.
14. Papadimitropoulos A, Piccinini E, Brachat S, Braccini A, Wendt D, Barbero A, et al. Expansion of Human Mesenchymal Stromal Cells from Fresh Bone Marrow in a 3D Scaffold- Based System under Direct Perfusion. PLoS One 2014; 9(7): e102359.
15. Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, et al. Minimal Criteria for Defining Multipotent Mesenchymal Stromal Cells. The International Society for Cellular Therapy Position Statement. Cytotherapy 2006; 8(4): 315–7.
16. Choi YH, Kurtz A, Stamm C. Mesenchymal Stem Cells for Cardiac Cell Therapy. Hum Gene Ther. 2011; 22(1): 3–17.
17. Schachtele S, Clouser C, Aho J. Markers and Methods to Verify Mesenchymal Stem Cell Identity, Potency, and Quality. WHITE PAPER, R&D Systems, Inc. Available from: https://resources.rndsystems.com/images/site/wp-msc-13763.pdf
18. Shachpazyan NR, Astrelina TA, Yakovleva MV. Mesenchymalstem Cells from Various Human Tissues: Biological Properties, Assessment of Quality and Safetyfor Clinical Use. Cellular Transplantation and Tissue Engineering 2012; 7(1): 23–33 (In Russ.)
19. Prockop DJ, Olson SD. Clinical Trials with Adult Stem/Progenitor Cells for Tissue Repair: Let’s not Overlook Some Essential Precautions. Blood 2007; 109(8): 3147–51.
20. Haniffa MA, Collin MP, Buckley CD, Dazzi F. Mesenchymal Stem Cells: The Fibroblasts’ New Clothes? Haematologica 2009; 94(2): 258–63.
21. Kundrotas G. Surface Markers Distinguishing Mesenchymal Stem Cells from Fibroblasts. Acta Medica Lituanica 2012; 19(2): 75–9.
22. Sakaguchi Y, Sekiya I, Yagishita K, Muneta T. Comparison of Human Stem Cells Derived from Various Mesenchymal Tissues: Superiority of Synovium as a Cell Source. Arthritis Rheum. 2005; 52(8): 2521–9.
23. Li Q, Tang J, Wang R, Bei C, Xin L, Zeng Y, Tang X. Comparing the Chondrogenic Potential in Vivo of Autogeneic Mesenchymal Stem Cells Derived from Different Tissues. Artif Cells Blood Substit Immobil Biotechnol. 2011; 39(1): 31–8.
24. Boxall SA, Jones E. Markers for Characterization of Bone Marrow Multipotential Stromal Cells. Stem Cells International 2012; 2012. Available from: https://www.hindawi.com/journals/sci/2012/975871/cta/
25. Quirici N, Scavullo C, de Girolamo L, Lopa S, Arrigoni E, Deliliers GL, Brini AT. Anti-L- NGFR and -CD34 Monoclonal Antibodies Identify Multipotent Mesenchymal Stem Cells in Human Adipose Tissue. Stem Cells Dev. 2010; 19(6): 915–25.
26. Arufe MC, De La Fuente A, Fuentes I, de Toro FJ, Blanco FJ. Chondrogenic Potential of Subpopulations of Cells Expressing Mesenchymal Stem Cell Markers Derived from Human Synovial Membranes. J Cell Biochem. 2010; 111(4): 834–45.
27. Kurth TB, Dell’Accio F, Crouch V, Augello A, Sharpe PT, De Bari C. Functional Mesenchymal Stem Cell Niches in Adult Mouse Knee Joint Synovium in Vivo. Arthritis Rheum. 2011; 63(5): 1289–1300.
28. Mikami Y, Ishii Y, Watanabe N, Shirakawa T, Suzuki S, Irie S, et al. CD271/p75NTR Inhibits the Differentiation of Mesenchymal Stem Cells into Osteogenic, Adipogenic, Chondrogenic, and Myogenic Lineages. Stem Cells Dev. 2011; 20(5): 901–13.
29. Moretti P, Hatlapatka T, Marten D, Lavrentieva A, Majore I, Hass R, Kasper C. Mesenchymal Stromal Cells Derived from Human Umbilical Cord Tissues: Primitive Cells with Potential for Clinical And Tissue Engineering Applications. Adv Biochem Eng Biotechnol. 2010; 123: 29–54.
30. Schäffler A, Büchler C. Concise Review: Adipose Tissue-Derived Stromal Cells — Basic and Clinical Implications for Novel Cell-Based Therapies. Stem Cells 2007; 25(4): 818–27.
31. Domnina AP, Fridlianskaia II, Zemelko VI, Pugovkina NA, Kovaleva ZV, Zenin VV, et al. Mesenchymal Stem Cells of Human Endometrium Do Not Undergo Spontaneous Transformation During Long-Term Cultivation. Tsitologiya 2013; 55(1): 69– 74 (In Russ.)
32. Shamanskaya TV, Osipova YeYu, Purbueva BB, Ustyugov AYu, Astrelina TA, Yakovleva MV, Rumyantsev SA. Ex Vivo Expansion of Mesenchymal Stem Cells in Different Culture Conditions (The Literature Review and Own Experience). Oncohematology 2010; (3): 65–71 (In Russ.)
33. Maleki M, Ghanbarvand F, Behvarz MR, Ejtemaei M, Ghadirkhomi E. Comparison of Mesenchymal Stem Cell Markers in Multiple Human Adult Stem Cells. Int J Stem Cells 2014 Nov; 7(2): 118–26.
34. Abdel-Latif A, Bolli R, Tleyjeh IM, Montori VM, Perin EC, Hornung CA, et al. Adult Bone Marrow-Derived Cells for Cardiac Repair: a Systematic Review and Meta-Analysis. Arch Intern Med. 2007; 167(10): 989–97.
35. Konoplyannikov MA, Kalsin VA, Averyanov AV. Stem Cells for the Therapy of Ischemic Heart Disease: Advances and Prospects. Clinical Practice 2012; (3): 63–77 (In Russ.)
36. Mansour S, Roy DC, Bouchard V, Nguyen BK, Stevens LM, Gobeil F, et al. COMPARE-AMI Trial: Comparison of Intracoronary Injection of CD133+ Bone Marrow Stem Cells to Placebo in Patients after Acute Myocardial Infarction and Left Ventricular Dysfunction: Study Rationale and Design. J Cardiovasc Transl Res. 2010; 3(2): 153–9.
37. Oh H, Bradfute SB, Gallardo TD, Nakamura T, Gaussin V, Mishina Y, et al. Cardiac Progenitor Cells from Adult Myocardium: Homing, Differentiation, and Fusion after Infarction. Proc Natl Acad Sci USA 2003; 100(21): 12313–8.
38. Valente M, Nascimento DS, Cumano A, Pinto-do-Ó P. Sca-1+ Cardiac Progenitor Cells and Heart-Making: a Critical Synopsis. Stem Cells Dev. 2014; 23(19): 2263–73.
39. Keith MC, Bolli R. «String theory» of C-Kit(Pos) Cardiac Cells: A New Paradigm Regarding the Nature of These Cells that May Reconcile Apparently Discrepant Results. Circ Res. 2015; 116(7): 1216–30.
40. Matsuura K, Nagai T, Nishigaki N, Oyama T, Nishi J, Wada H, et al. Adult Cardiac Sca-1- Positive Cells Differentiate into Beating Cardiomyocytes. J Biol Chem. 2004; 279(12): 11384–91.
41. Wang X, Hu Q, Nakamura Y, Lee J, Zhang G, From AH, Zhang J. The Role of the Sca- 1+/CD31- Cardiac Progenitor Cell Population in Postinfarction Left Ventricular Remodeling. Stem Cells 2006; 24(7): 1779–88.
42. Bolli R, Chugh AR, D’Amario D, Loughran JH, Stoddard MF, Ikram S, et al. Cardiac Stem Cells in Patients with Ischaemic Cardiomyopathy (SCIPIO): Initial Results of a Randomised Phase 1 Trial. Lancet 2011; 378(9806): 1847–57.
43. Zaruba MM, Soonpaa M, Reuter S, Field LJ. Cardiomyogenic Potential of C-Kit+- Expressing Cells Derived from Neonatal and Adult Mouse Hearts. Circulation 2010; 121(18): 1992– 2000.
44. American Type Culture Collection (ATCC) (In Russ.)] Available from: http://www.lgcstandards-atcc.org
45. Jackson CJ, Tønseth KA, Utheim TP. Cultured Epidermal Stem Cells in Regenerative Medicine. Stem Cell Res Ther. 2017; 8(1): 155.
46. Jensen KB, Watt FM. Single-Cell Expression Profiling of Human Epidermal Stem and Transit-Amplifying Cells: Lrig1 Is a Regulator of Stem Cell Quiescence. Proc Natl Acad Sci USA 2006; 103(32): 11958–63.
47. Tan DW, Jensen KB, Trotter MW, Connelly JT, Broad S, Watt FM. Single-Cell Gene Expression Profiling Reveals Functional Heterogeneity of Undifferentiated Human Epidermal Cells. Development 2013; 140(7):1433–44.
48. Australian Public Assessment Report for Remestemcel-L, Ex Vivo Adult Human Mesenchymal Stem Cells. Australian Government, Department of Health, Therapeutic Goods Administration, 2015. Available from: https://www.tga.gov.au/sites/default/files/auspar-remestemcel-l-150315.pdf
49. Bozhokin MS, Bozhkova SA, Netylko GI. Possibilities of Current Cellular Technologies for Articular Cartilage Repair (Analytical Review). Traumatology and Orthopedics of Russia 2016; 22(3): 122–34 (In Russ.)
50. Gille J, Schuseil E, Wimmer J, Gellissen J, Schulz AP, Behrens P. Mid-Term Results of Autologous Matrix-Induced Chondrogenesis for Treatment of Focal Cartilage Defects in the Knee. Knee Surg Sports Traumatol Arthrosc. 2010; 18(11): 1456–64.
51. Vasiliadis HS, Danielson B, Ljungberg M, McKeon B, Lindahl A, Peterson L. Autologous Chondrocyte Implantation in Cartilage Lesions of the Knee: Long-Term Evaluation with Magnetic Resonance Imaging and Delayed Gadolinium- Enhanced Magnetic Resonance Imaging Technique. Am. J. Sports. Med. 2010; 38(5): 943–49.
52. Camarero-Espinosa S, Rothen-Rutishauser B, Foster EJ, Weder C. Articular Cartilage: from Formation to Tissue Engineering. Biomater Sci. 2016; 4(5): 734–67.
53. Tigenix NV, Luyten F, De Bari C, Dell’Accio F. Marker Genes for Use in the Identification of Chondrocyte Phenotypic Stability and in the Screening of Factors Influencing Cartilage Production. Patent of the Russian Federation, No. 2508548; 2014 (In Russ.)
54. Isaev AA, Prikhodko AV, Zorin VL, et al. Medical technology «Fence, Transportation, Isolation, Cultivation, Cryopreservation, Storage and Use of Autologous Fibroblasts for Correction of Age-Related and Cicatrical Skin Changes». FS № 2009/398 dated 21.07.2010 (In Russ.)
55. Zorin VL, Zorina AI, Petrakova OS, Cherkasov VR. Dermal Fibroblasts for Skin Defects Therapy. Cell Transplantology and Tissue Engineering 2009; 4(4): 26–40 (In Russ.)
56. Zorin V, Zorina A, Cherkasov V, Kopnin P, Deev R, Isaev A, et al. Application of Autologous Dermal Fibroblasts for Correction of Age- Related Changes of Skin: the Year of Clinical Observations. Aesthetic Medicine 2012; 11(2): 171–82 (In Russ.)
57. Committee for Medicinal Products for Human Use (CHMP). Guideline on Potency Testing of Cell Based Immunotherapy Medicinal Products for the Treatment of Cancer (EMEA/CHMP/BWP/271475/2006). Available from: http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003814.pdf
58. Méndez-Hermida F. Approaches to the Non-Clinical Development of Advanced Therapy Medicinal Products. SME Workshop: Focus on Non-Clinical Aspects. European Medicines Agency, London, United Kingdom; 2016.
59. Nazarkina ZhK, Laktionov PP. Preparation of Dendritic Cells for Cancer Immunotherapy. Biomedical Chemistry 2015; 61(1): 30–40 (In Russ.)
Review
For citations:
Trusov G.A., Chaplenko A.A., Semenova I.S., Melnikova E.V., Olefir Yu.V. Use of Flow Cytometry for Quality Evaluation of Biomedical Cell Products. BIOpreparations. Prevention, Diagnosis, Treatment. 2018;18(1):16-24. (In Russ.) https://doi.org/10.30895/2221-996X-2018-18-1-16-24
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