Expansion, harvest and cryopreservation of human mesenchymal stem cells in a serum-free microcarrier process

Biotechnology and Bioengineering

Volumn 112, Issue 8, 2015, Pages 1696-1707

  Heathman, Thomas R J ^a   Glyn, Veronica A M ^a   Picken, Andrew ^a   Rafiq, Qasim A ^a,b   Coopman, Karen ^a   Nienow, Alvin W ^a,c   Kara, Bo ^d   Hewitt, Christopher J ^a,b  

^a LOUGHBOROUGH UNIVERSITY   (United Kingdom)

^b ASTON UNIVERSITY   (United Kingdom)

^c UNIVERSITY OF BIRMINGHAM   (United Kingdom)

^d Fujifilm Diosynth Biotechnologies   (United Kingdom)

Author keywords

Cryopreservation; Harvest; Human mesenchymal stem cell; Microcarrier expansion; Regenerative medicine; Serum free

Indexed keywords

ANIMALS; BIOLOGICAL MATERIALS PRESERVATION; BODY FLUIDS; CELL CULTURE; CELLS; COST EFFECTIVENESS; CYTOLOGY; HARVESTING; MANUFACTURE; OPTIMIZATION;

CRYO-PRESERVATION; HUMAN MESENCHYMAL STEM CELLS; MICROCARRIERS; REGENERATIVE MEDICINE; SERUM FREE;

STEM CELLS;

AMMONIA; LACTATE DEHYDROGENASE; PROTEIN; CULTURE MEDIUM; MICROSPHERE;

ADIPOCYTE; AMMONIA FORMATION; ANALYTIC METHOD; ANTIGEN BINDING; ARTICLE; CELL ADHESION; CELL COUNTING; CELL DENSITY; CELL ELONGATION; CELL ENLARGEMENT; CELL GROWTH; CELL POPULATION; CELL SEPARATION; CELL STRUCTURE; CELL VIABILITY; COLONY FORMING UNIT; CONTROLLED STUDY; CRYOPRESERVATION; CULTURE MEDIUM; EXTRACELLULAR MATRIX; GROWTH RATE; HUMAN; HUMAN CELL; MESENCHYMAL STEM CELL; MICROCARRIER CULTURE; MONOLAYER CULTURE; NORMAL HUMAN; PILOT STUDY; PROCEDURES CONCERNING CELLS; PROCESS DEVELOPMENT; PROCESS OPTIMIZATION; PROTEIN SECRETION; SERUM FREE MICROCARRIER CULTURE; STEM CELL CULTURE; STEM CELL EXPANSION; STEM CELL HARVEST; SURFACE AREA; SUSPENSION CELL CULTURE; CELL PROLIFERATION; CELL SURVIVAL; CHEMISTRY; CULTURE TECHNIQUE; MESENCHYMAL STROMA CELL; PHYSIOLOGY; PRESERVATION; PROCEDURES; STEM CELL;

ANIMALIA;

CELL CULTURE TECHNIQUES; CELL PROLIFERATION; CELL SURVIVAL; CRYOPRESERVATION; CULTURE MEDIA, SERUM-FREE; HUMANS; MESENCHYMAL STROMAL CELLS; MICROSPHERES; PILOT PROJECTS; PRESERVATION, BIOLOGICAL; STEM CELLS;

EID: 84932197083     PISSN: 00063592     EISSN: 10970290     Source Type: Journal    
DOI: 10.1002/bit.25582     Document Type: Article

References (38)

1. Baraniak PR, Cooke MT, Saeed R, Kinney MA, Fridley KM, McDevitt TC. 2012. Stiffening of human mesenchymal stem cell spheroid microenvironments induced by incorporation of gelatin microparticles. J Mech Behav Biomed Mater 11:63-71.
2. Brindley DA, Davie NL, Culme-Seymour EJ, Mason C, Smith DW, Rowley JA. 2012. Peak serum: Implications of serum supply for cell therapy manufacturing. Regen Med 7:7-13.
3. Caplan AI. 1991. Mesenchymal stem cells. J Orthop Res 9:641-650.
4. Caplan AI, Dennis JE. 2006. Mesenchymal stem cells as trophic mediators. J Cell Biochem 98:1076-1084.
5. Carmen J, Burger SR, McCaman M, Rowley JA. 2012. Developing assays to address identity, potency, purity and safety: Cell characterization in cell therapy process development. Regen Med 7:85-100.
6. Chan AK, Heathman TR, Coopman K, Hewitt CJ. 2014. Multiparameter flow cytometry for the characterisation of extracellular markers on human mesenchymal stem cells. Biotechnol Lett 36:731-741.
7. Crapnell K, Blaesius R, Hastings A, Lennon DP, Caplan AI, Bruder SP. 2013. Growth, differentiation capacity, and function of mesenchymal stem cells expanded in serum-free medium developed via combinatorial screening. Exp Cell Res 319:1409-1418.
8. Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, Deans R, Keating A, Prockop D, Horwitz E. 2006. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 8:315-317.
9. dos Santos F, Campbell A, Fernandes-Platzgummer A, Andrade PZ, Gimble JM, Wen Y, Boucher S, Vemuri MC, da Silva CL, Cabral JMS. 2014. A xenogeneic-free bioreactor system for the clinical-scale expansion of human mesenchymal stem/stromal cells. Biotechnology and Bioengineering 111:1116-1127.
10. Dreher L, Elvers-Hornung S, Brinkmann I, Huck V, Henschler R, Gloe T, Kluter H, Bieback K. 2013. Cultivation in human serum reduces adipose tissue-derived mesenchymal stromal cell adhesion to laminin and endothelium and reduces capillary entrapment. Stem Cells Dev 22:791-803.
11. FDA. 2008. Content and Review of Chemistry, Manufacturing, and Control (CMC) Information for Human Gene Therapy Investigational New Drug Applications (INDs).
12. Ge J, Guo L, Wang S, Zhang Y, Cai T, Zhao RC, Wu Y. 2014. The size of mesenchymal stem cells is a significant cause of vascular obstructions and stroke. Stem Cell Rev 10:295-303.
13. Hare JM, Traverse JH, Henry TD, Dib N, Strumpf RK, Schulman SP, Gerstenblith G, DeMaria AN, Denktas AE, Gammon RS, Hermiller JB, Reisman MA, Schaer GL, Sherman W. 2009. A randomized, double-blind, placebo-controlled, dose-escalation study of intravenous adult human mesenchymal stem cells (prochymal) after acute myocardial infarction. J Am Coll Cardiol 54:2277-2286.
14. Hayman EG, Pierschbacher MD, Suzuki S, Ruoslahti E. 1985. Vitronectin-a major cell attachment-promoting protein in fetal bovine serum. Exp Cell Res 160:245-258.
15. Heathman TRJ, Nienow AW, McCall MJ, Coopman K, Kara B, Hewitt CJ. 2014. The translation of cell-based therapies: Clinical landscape and manufacturing challenges. Regen Med 10:49-64.
16. Heiskanen A, Satomaa T, Tiitinen S, Laitinen A, Mannelin S, Impola U, Mikkola M, Olsson C, Miller-Podraza H, Blomqvist M, Olonen A, Salo H, Lehenkari P, Tuuri T, Otonkoski T, Natunen J, Saarrinen J, Laine J. 2007. N-glycolylneuraminic acid xenoantigen contamination of human embryonic and mesenchymal stem cells is substantially reversible. Stem Cells 25:197-202.
17. Higuera GA, Schop D, Spitters TW, van Dijkhuizen-Radersma R, Bracke M, de Bruijn JD, Martens D, Karperien M, van Boxtel A, van Blitterswijk CA. 2012. Patterns of amino acid metabolism by proliferating human mesenchymal stem cells. Tissue Eng Part A 18:654-664.
18. Huttenlocher A, Horwitz AR. 2011. Integrins in cell migration. Cold Spring Harb Perspect Biol 3:005074.
19. ICH. 2005 Quality Risk Management Q9. In: Group IEW, editor.
20. Lavrentieva A, Majore I, Kasper C, Hass R. 2010. Effects of hypoxic culture conditions on umbilical cord-derived human mesenchymal stem cells. Cell Communication 8:1-9.
21. Liu Y, Xu X, Ma X, Martin-Rendon E, Watt S, Cui Z. 2010. Cryopreservation of human bone marrow-derived mesenchymal stem cells with reduced dimethylsulfoxide and well-defined freezing solutions. Biotechnol Prog 26:1635-1643.
22. Moll G, Alm JJ, Davies LC, von Bahr L, Heldring N, Stenbeck-Funke L, Hamad OA, Hinsch R, Ignatowicz L, Locke M, Lönnies H, Lambris JD, Teramura Y, Nilsson-Ekdahl K, Nilsson B, Le Blanc K. 2014. Do cryopreserved mesenchymal stromal cells display impaired immunomodulatory and therapeutic properties. Stem Cells 32:2430-2442.
23. Nienow AW. 2006. Reactor engineering in large scale animal cell culture. Cytotechnology 50:9-33.
24. Nienow AW, Rafiq QA, Coopman K, Hewitt CJ. 2014. A potentially scalable method for the harvesting of hMSCs from microcarriers. Biochemical Engineering Journal 85:79-88.
25. Pal R, Hanwate M, Totey SM. 2008. Effect of holding time, temperature and different parenteral solutions on viability and functionality of adult bone marrow-derived mesenchymal stem cells before transplantation. J Tissue Eng Regen Med 2:436-444.
26. Pattasseril J, Varadaraju H, Lock L, Rowley JA. 2013. Downstream technology landscape for large-scale therapeutic cell processing. BioProcess International 11:38-47.
27. Pochampally R. 2008. Colony forming unit assays for MSCs. Methods Mol Biol 449:83-91.
28. Rafiq QA, Brosnan KM, Coopman K, Nienow AW, Hewitt CJ. 2013. Culture of human mesenchymal stem cells on microcarriers in a 5l stirred-tank bioreactor. Biotechnol Lett 35:1233-1245.
29. Rowley J, Abraham E, Campbell A, Brandwein H, Oh S. 2012. Meeting lot-size challenges of manufacturing adherent cells for therapy. BioProcess International 10:16-22.
30. Santos F, Andrade PZ, Abecasis MM, Gimble JM, Chase LG, Campbell AM, Boucher S, Vemuri MC, Silva CL, Cabral JM. 2011. Toward a clinical-grade expansion of mesenchymal stem cells from human sources: A microcarrier-based culture system under xeno-free conditions. Tissue Eng Part C Methods 17:1201-1210.
31. Schellenberg A, Stiehl T, Horn P, Joussen S, Pallua N, Ho AD, Wagner W. 2012. Population dynamics of mesenchymal stromal cells during culture expansion. Cytotherapy 14:401-411.
32. Schop D, Janssen FW, van Rijn LD, Fernandes H, Bloem RM, de Bruijn JD, van Dijkhuizen-Radersma R. 2009. Growth, metabolism, and growth inhibitors of mesenchymal stem cells. Tissue Eng Part A 15:1877-1886.
33. Sethe S, Scutt A, Stolzing A. 2006. Aging of mesenchymal stem cells. Ageing Res Rev 5:91-116.
34. Shaffer AL, Shapiro-Shelef M, Iwakoshi NN, Lee AH, Qian SB, Zhao H, Yu X, Yang L, Tan BK, Rosenwald A, Hurt EM, Petroulakis E, Sonenberg N, Yewdell JW, Calame K, Glimcher LH, Staudt LM. 2004. XBP1, downstream of Blimp-1, expands the secretory apparatus and other organelles, and increases protein synthesis in plasma cell differentiation. Immunity 21:81-93.
35. Spees JL, Gregory CA, Singh H, Tucker HA, Peister A, Lynch PJ, Hsu SC, Smith J, Prockop DJ. 2004. Internalized antigens must be removed to prepare hypoimmunogenic mesenchymal stem cells for cell. Mol Ther 9:747-756.
36. Wagner W, Wein F, Seckinger A, Frankhauser M, Wirkner U, Krause U, Blake J, Schwager C, Eckstein V, Ansorge W, Ho AD. 2005. Comparative characteristics of mesenchymal stem cells from human bone marrow, adipose tissue, and umbilical cord blood. Exp Hematol 33:1402-1416.
37. Wappler J, Rath B, Laufer T, Heidenreich A, Montzka K. 2013. Eliminating the need of serum testing using low serum culture conditions for human bone marrow-derived mesenchymal stromal cell expansion. Biomed Eng Online 12:15.
38. Wuchter P, Bieback K, Schrezenmeier H, Bornhauser M, Muller LP, Bonig H, Wagner W, Meisel R, Pavel P, Tonn T, Lang P, Müller I, Renner M, Malcherek G, Saffrich R, Buss EC, Horn P, Rojewski M, Schmitt A, Ho AD, Sanzenbacher R, Schmitt M. 2015. Standardization of Good Manufacturing Practice-compliant production of bone marrow-derived human mesenchymal stromal cells for immunotherapeutic applications. Cytotherapy 17:128-139.