Large-scale expansion and exploitation of pluripotent stem cells for regenerative medicine purposes: Beyond the T flask

Regenerative Medicine

Volumn 7, Issue 1, 2012, Pages 71-84

  Want, Andrew J ^a   Nienow, Alvin W ^a,b   Hewitt, Christopher J ^a   Coopman, Karen ^a  

^a LOUGHBOROUGH UNIVERSITY   (United Kingdom)

^b UNIVERSITY OF BIRMINGHAM   (United Kingdom)

Author keywords

automation; large scale; microcarriers; pluripotent stem cells; scale out; scale up; separation; suspension culture

Indexed keywords

ALLOGENEIC STEM CELL TRANSPLANTATION; AUTOLOGOUS STEM CELL TRANSPLANTATION; BIOCOMPATIBILITY; CELL ADHESION; CELL AGGREGATION; CELL DIFFERENTIATION; CELL ISOLATION; CELL REGENERATION; CELL RENEWAL; CLINICAL PRACTICE; CULTURE OPTIMIZATION; CULTURE TECHNIQUE; EXTRACELLULAR MATRIX; HUMAN; MICROCARRIER CULTURE; NONHUMAN; PLURIPOTENT STEM CELL; PRIORITY JOURNAL; REGENERATIVE ABILITY; REGENERATIVE MEDICINE; REVIEW; SCALE UP; STEM CELL EXPANSION; STEM CELL TRANSPLANTATION; STIRRED REACTOR; SUSPENSION CELL CULTURE; T FLASK CULTURE; TISSUE ENGINEERING;

CELL CULTURE TECHNIQUES; CELL DIFFERENTIATION; CELL PROLIFERATION; FEASIBILITY STUDIES; HUMANS; PLURIPOTENT STEM CELLS; REGENERATIVE MEDICINE;

EID: 83655212727     PISSN: 17460751     EISSN: 1746076X     Source Type: Journal    
DOI: 10.2217/rme.11.101     Document Type: Review

References (102)

1. Barker C, Culme-Seymour E, Dalton S, Hayek A, Genbacev O. The year in regenerative medicine. Regen. Med. 6, 21-30 (2011).
2. Sommerfeld S, Strube J. Challenges in biotechnology production - generic processes and process optimization for monoclonal antibodies. Chem. Eng. Processing 44, 1123-1137 (2005). (Pubitemid 41379671)
3. Dwyer JL. Scaling up bio-product separation with high performance liquid chromatography. Nat. Biotechnol. 2, 957-964 (1984). (Pubitemid 15090592)
4. Chandra S, Groener A, Feldman F. Effectiveness of alternative treatments for reducing potential viral contaminants from plasma-derived products. Thromb. Res. 105, 391-400 (2002). (Pubitemid 34621256)
5. Thomas RJ, Anderson D, Chandra A et al. Automated, scalable culture of human embryonic stem cells in feeder-free conditions. Biotechnol. Bioeng. 102, 1636-1644 (2009).
6. Terstegge S, Laufenberg I, Pochert J et al. Automated maintenance of embryonic stem cell cultures. Biotechnol. Bioeng. 96, 195-201 (2007). (Pubitemid 46036171)
7. Allegrucci C, Young LE. Differences between human embryonic stem cell lines. Hum. Reprod. Update 13, 103-120 (2007). (Pubitemid 46323190)
8. Thomson JA, Itskovitz-Eldor J, Shapiro SS et al. Embryonic stem cell lines derived from human blastocysts. Science 282, 1145-1147 (1998). (Pubitemid 28516247)
9. Evans MJ, Kaufman MH. Establishment in culture of pluripotential cells from mouse embryos. Nature 292, 154-156 (1981). (Pubitemid 11050741)
10. Richards M, Tan S, Fong CY, Biswas A, Chan WK, Bongso A. Comparative evaluation of various human feeders for prolonged undifferentiated growth of human embryonic stem cells. Stem Cells 21, 546-556 (2003). (Pubitemid 37444111)
11. Hovatta O, Mikkola M, Gertow K et al. A culture system using human foreskin fibroblasts as feeder cells allows production of human embryonic stem cells. Hum. Reprod. 18, 1404-1409 (2003). (Pubitemid 36840945)
12. Stojkovic P, Lako M, Stewart R et al. An autogeneic feeder cell system that efficiently supports growth of undifferentiated human embryonic stem cells. Stem Cells 23, 306-314 (2005). (Pubitemid 40404449)
13. Denning C, Allegrucci C, Priddle H et al. Common culture conditions for maintenance and cardiomyocyte differentiation of the human embryonic stem cell lines, BG01 and HUES-7. Int. J. Dev. Biol. 50, 27-37 (2006). (Pubitemid 43145107)
14. Xu C, Inokuma MS, Denham J et al. Feeder-free growth of undifferentiated human embryonic stem cells. Nat. Biotechnol. 19, 971-974 (2001). (Pubitemid 32947578)
15. Totonchi M, Taei A, Seifinejad A et al. Feeder- and serum-free establishment and expansion of human induced pluripotent stem cells. Int. J. Dev. Biol. 54, 877-886 (2010).
16. Kleinman HK, Martin GR. Matrigel: basement membrane matrix with biological activity. Semin. Cancer Biol. 15, 378-386 (2005). (Pubitemid 41140305)
17. Hughes CS, Postovit LM, Lajoie GA. Matrigel: a complex protein mixture required for optimal growth of cell culture. Proteomics 10, 1886-1890 (2010).
18. Ludwig TE, Levenstein ME, Jones JM et al. Derivation of human embryonic stem cells in defined conditions. Nat. Biotechnol. 24, 185-187 (2006). (Pubitemid 43221701)
19. McDevitt TC, Palecek SP. Innovation in the culture and derivation of pluripotent human stem cells. Curr. Opin. Biotechnol. 19, 527-533 (2008).
20. International Stem Cell Initiative Consortium; Akopian V, Andrews PW, Beil S et al. Comparison of defined culture systems for feeder cell free propagation of human embryonic stem cells. In Vitro Cell. Dev. Biol. Anim. 46, 247-258 (2010).
21. Amit M, Shariki C, Margulets V, Itskovitz-Eldor J. Feeder layer- and serum-free culture of human embryonic stem cells. Biol. Reprod. 70, 837-845 (2004). (Pubitemid 38233724)
22. Rodin S, Domogatskaya A, Strom S et al. Long-term self-renewal of human pluripotent stem cells on human recombinant laminin 511. Nat. Biotechnol. 28, 611-615 (2010).
23. Braam SR, Zeinstra L, Litjens S et al. Recombinant vitronectin is a functionally defined substrate that supports human embryonic stem cell self-renewal via alphavbeta5 integrin. Stem Cells 26, 2257-2265 (2008).
24. Kolhar P, Kotamraju VR, Hikita ST, Clegg DO, Ruoslahti E. Synthetic surfaces for human embryonic stem cell culture. J. Biotechnol. 146, 143-146 (2010).
25. Li YJ, Chung EH, Rodriguez RT, Firpo MT, Healy KE. Hydrogels as artificial matrices for human embryonic stem cell self-renewal. J. Biomed. Mat. Res. Part A 79(1), 1-5 (2006). (Pubitemid 44452848)
26. Mahlstedt MM, Anderson D, Sharp JS et al. Maintenance of pluripotency in human embryonic stem cells cultured on a synthetic substrate in conditioned medium. Biotechnol. Bioeng. 105, 130-140 (2010).
27. Melkoumian Z, Weber JL, Weber DM et al. Synthetic peptide-acrylate surfaces for long-term self-renewal and cardiomyocyte differentiation of human embryonic stem cells. Nat. Biotechnol. 28, 606-610 (2010).
28. Azarin SM, Palecek SP. Development of scalable culture systems for human embryonic stem cells. Biochem. Eng. J. 48, 378 (2010).
29. Watanabe K, Ueno M, Kamiya D et al. A ROCK inhibitor permits survival of dissociated human embryonic stem cells. Nat. Biotechnol. 25, 681-686 (2007). (Pubitemid 46897207)
30. Brimble SN, Zeng X, Weiler DA et al. Karyotypic stability, genotyping, differentiation, feeder-free maintenance, and gene expression sampling in three human embryonic stem cell lines derived prior to August 9, 2001. Stem Cells Dev. 13, 585-597 (2004). (Pubitemid 40052635)
31. Pakzad M, Totonchi M, Taei A, Seifinejad A, Hassani SN, Baharvand H. Presence of a ROCK inhibitor in extracellular matrix supports more undifferentiated growth of feeder-free human embryonic and induced pluripotent stem cells upon passaging. Stem Cell Rev. 6, 96-107 (2010).
32. Priddle H, Allegrucci C, Burridge P et al. Derivation and characterization of the human embryonic stem cell lines, NOTT1 and NOTT2. In Vitro Cell. Dev. Biol. Anim. 46, 367-375 (2010).
33. Chin AC, Padmanabhan J, Oh SK, Choo AB. Defined and serum-free media support undifferentiated human embryonic stem cell growth. Stem Cells Dev. 19, 753-761 (2010).
34. Mallon BS, Park KY, Chen KG, Hamilton RS, McKay RDG. Toward xeno-free culture of human embryonic stem cells. Int. J. Biochem. Cell Biol. 38, 1063-1075 (2006).
35. van Wezel AL. Growth of cell-strains and primary cells on micro-carriers in homogeneous culture. Nature 216, 64-65 (1967).
36. Nienow AW. Reactor engineering in large scale animal cell culture. Cytotechnology 50, 9-33 (2006).
37. Schutt C, Furll B, Stelter F, Jack RS, Witt S. CHO transfectants produce large amounts of recombinant protein in suspension culture. J. Immunol. Methods 204, 99-102 (1997). (Pubitemid 27192316)
38. Kumar N, Gammell P, Meleady P, Henry M, Clynes M. Differential protein expression following low temperature culture of suspension CHO-K1 cells. BMC Biotechnol. 8, 42 (2008).
39. Abranches E, Bekman E, Henrique D, Cabral JMS. Expansion of mouse embryonic stem cells on microcarriers. Biotechnol. Bioeng. 96, 1211-1221 (2007). (Pubitemid 46648679)
40. Fernandes AM, Diogo MM, da Silva CL, Henrique D, Cabral JMS. Mouse embryonic stem cell expansion in a microcarrier-based stirred culture system. J. Biotechnol. 132, 227-236 (2007). (Pubitemid 47599708)
41. Niebruegge S, Nehring A, Bar H, Schroeder M, Zweigerdt R, Lehmann J. Cardiomyocyte production in mass suspension culture: embryonic stem cells as a source for great amounts of functional cardiomyocytes. Tissue Eng. Part A 14, 1591-1601 (2008).
42. zur Nieden NI, Cormier JT, Rancourt DE, Kallos MS. Embryonic stem cells remain highly pluripotent following long-term expansion as aggregates in suspension bioreactors. J. Biotechnol. 129, 421-432 (2007). (Pubitemid 46560150)
43. Fernandes AM, Marinho PA, Sartore RC et al. Successful scale-up of human embryonic stem cell production in a stirred microcarrier culture system. Braz. J. Med. Biol. Res. 42, 515-522 (2009).
44. Phillips BW, Horne R, Lay TS, Rust WL, Teck TT, Crook JM. Attachment and growth of human embryonic stem cells on microcarriers. J. Biotechnol. 138, 24-32 (2008).
45. Storm MP, Orchard CB, Bone HK, Chaudhuri JB, Welham MJ. Three-dimensional culture systems for the expansion of pluripotent embryonic stem cells. Biotechnol. Bioeng. 107(4), 683-695 (2010).
46. Oh SK, Chen AK, Mok Y et al. Long-term microcarrier suspension cultures of human embryonic stem cells. Stem Cell Res. 2, 219-230 (2009).
47. James D, Levine AJ, Besser D, Hemmati-Brivanlou A. TGFbeta/activin/ nodal signaling is necessary for the maintenance of pluripotency in human embryonic stem cells. Development 132, 1273-1282 (2005). (Pubitemid 40528787)
48. Levenstein ME, Ludwig TE, Xu RH et al. Basic fibroblast growth factor support of human embryonic stem cell self-renewal. Stem Cells 24, 568-574 (2006). (Pubitemid 44464760)
49. Chen AK, Chen X, Choo ABH, Reuveny S, Oh SKW. Critical microcarrier properties affecting the expansion of undifferentiated human embryonic stem cells. Stem Cell Res. 7(2), 97-111 (2011).
50. Serra M, Brito C, Sousa MF et al. Improving expansion of pluripotent human embryonic stem cells in perfused bioreactors through oxygen control. J. Biotechnol. 148, 208-215 (2010).
51. Ezashi T, Das P, Roberts RM. Low O2 tensions and the prevention of differentiation of hES cells. Proc. Natl Acad. Sci. USA 102, 4783-4788 (2005). (Pubitemid 40471531)
52. Prasad SM, Czepiel M, Cetinkaya C et al. Continuous hypoxic culturing maintains activation of Notch and allows long-term propagation of human embryonic stem cells without spontaneous differentiation. Cell Prolif. 42, 63-74 (2009).
53. Abaci HE, Truitt R, Luong E, Drazer G, Gerecht S. Adaptation to oxygen deprivation in cultures of human pluripotent stem cells, endothelial progenitor cells, and umbilical vein endothelial cells. Am. J. Physiol. Cell. Physiol. 298, C1527-C1537 (2010).
54. Chen HF, Kuo HC, Chen W, Wu FC, Yang YS, Ho HN. A reduced oxygen tension (5%) is not beneficial for maintaining human embryonic stem cells in the undifferentiated state with short splitting intervals. Hum. Reprod. 24, 71-80 (2009).
55. Fischer B, Bavister BD. Oxygen tension in the oviduct and uterus of rhesus monkeys, hamsters and rabbits. J. Reprod. Fertil. 99, 673-679 (1993). (Pubitemid 24052018)
56. Aunins JG, Glazomitsky K, Buckland BC. Cell culture reactor design: known and unknown. In: Proc. 3rd Int. Conf. on Bioreactors and Bioprocess Fluid Dynamics. Nienow AW (Ed.). Mechanical Engineering Publications Ltd, London, UK, 175-190 (1993).
57. 2 and osmolality: intracellular pH, cell size, apoptosis, and metabolism. Biotechnol. Bioeng. 77, 369-380 (2002). (Pubitemid 34121531)
58. 2 in large scale and high-density CHO cell perfusion culture. Cytotechnology 22, 65-78 (1996). (Pubitemid 27133774)
59. 2 removal in large scale fed-batch cultures. Biotechnol. Prog. 19, 45-51 (2003). (Pubitemid 36219302)
60. Chaudhry MA, Bowen BD, Piret JM. Culture pH and osmolality influence proliferation and embryoid body yields of murine embryonic stem cells. Biochem. Eng. J. 45, 126-135 (2009).
61. Oh SK, Nienow AW, al-Rubeai M, Emery AN. Further studies of the culture of mouse hybridomas in an agitated bioreactor with and without continuous sparging. J. Biotechnol. 22, 245-270 (1992).
62. Wang JH, Thampatty BP. Mechanobiology of adult and stem cells. Int. Rev. Cell. Mol. Biol. 271, 301-346 (2008).
63. Leung HW, Chen A, Choo AB, Reuveny S, Oh SK. Agitation can induce differentiation of human pluripotent stem cells in microcarrier cultures. Tissue Eng. Part C Methods 17, 165-172 (2011).
64. Singh H, Mok P, Balakrishnan T, Rahmat SN, Zweigerdt R. Up-scaling single cell-inoculated suspension culture of human embryonic stem cells. Stem Cell Res. 4, 165-179 (2010).
65. Cameron CM, Hu WS, Kaufman DS. Improved development of human embryonic stem cell-derived embryoid bodies by stirred vessel cultivation. Biotechnol. Bioeng. 94, 938-948 (2006). (Pubitemid 44186901)
66. Gerecht-Nir S, Cohen S, Itskovitz-Eldor J. Bioreactor cultivation enhances the efficiency of human embryoid body (hEB) formation and differentiation. Biotechnol. Bioeng. 86, 493-502 (2004). (Pubitemid 38679767)
67. Schulz TC, Noggle SA, Palmarini GM et al. Differentiation of human embryonic stem cells to dopaminergic neurons in serum-free suspension culture. Stem Cells 22, 1218-1238 (2004). (Pubitemid 39636400)
68. Yirme G, Amit M, Laevsky I, Osenberg S, Itskovitz-Eldor J. Establishing a dynamic process for the formation, propagation, and differentiation of human embryoid bodies. Stem Cells Dev. 17, 1227-1241 (2008).
69. Jing D, Parikh A, Tzanakakis ES. Cardiac cell generation from encapsulated embryonic stem cells in static and scalable culture systems. Cell Transplant. 19, 1397-1412 (2010).
70. Olmer R, Haase A, Merkert S et al. Long-term expansion of undifferentiated human iPS and ES cells in suspension culture using a defined medium. Stem Cell Res. 5, 51-64 (2010).
71. Kehoe DE, Jing D, Lock LT, Tzanakakis ES. Scalable stirred-suspension bioreactor culture of human pluripotent stem cells. Tissue Eng. Part A 16, 405-421 (2010).
72. Steiner D, Khaner H, Cohen M et al. Derivation, propagation and controlled differentiation of human embryonic stem cells in suspension. Nat. Biotechnol. 28, 361-364 (2010).
73. Bauwens CL, Peerani R, Niebruegge S et al. Control of human embryonic stem cell colony and aggregate size heterogeneity influences differentiation trajectories. Stem Cells 26, 2300-2310 (2008).
74. Choo A, Padmanabhan J, Chin A, Fong WJ, Oh SKW. Immortalized feeders for the scale-up of human embryonic stem cells in feeder and feeder-free conditions. J. Biotechnol. 122, 130-141 (2006). (Pubitemid 43248722)
75. Kaneko Y, Sato R, Aoyagi H. Evaluation of Chinese hamster ovary cell stability during repeated batch culture for large scale antibody production. J. Biosci. Bioeng. 109, 274-280 (2010).
76. Draper JS, Smith K, Gokhale P et al. Recurrent gain of chromosomes 17q and 12 in cultured human embryonic stem cells. Nat. Biotechnol. 22, 53-54 (2004). (Pubitemid 38057956)
77. Clark AT, Rodriguez RT, Bodnar MS et al. Human STELLAR, NANOG, and GDF3 genes are expressed in pluripotent cells and map to chromosome 12p13, a hotspot for teratocarcinoma. Stem Cells 22, 169-179 (2004). (Pubitemid 38282632)
78. Harrison NJ, Barnes J, Jones M, Baker D, Gokhale PJ, Andrews PW. CD30 expression reveals that culture adaptation of human embryonic stem cells can occur through differing routes. Stem Cells 27, 1057-1065 (2009).
79. Sun X, Long X, Yin Y et al. Similar biological characteristics of human embryonic stem cell lines with normal and abnormal karyotypes. Hum. Reprod. 23, 2185-2193 (2008).
80. Hewitt CJ, Nienow AW. The scale-up of microbial batch and fed-batch fermentation processes. Adv. Appl. Microbiol. 62, 105-135 (2007). (Pubitemid 47380497)
81. Fong CY, Peh GS, Gauthaman K, Bongso A. Separation of SSEA 4 and TRA 1 60 labelled undifferentiated human embryonic stem cells from a heterogeneous cell population using magnetic-activated cell sorting (MACS) and fluorescence- activated cell sorting (FACS). Stem Cell Rev. 5(1), 72-80 (2009).
82. D'Amour KA, Bang AG, Eliazer S et al. Production of pancreatic hormone-expressing endocrine cells from human embryonic stem cells. Nat. Biotechnol. 24, 1392-1401 (2006). (Pubitemid 44722103)
83. Burridge PW, Anderson D, Priddle H et al. Improved human embryonic stem cell embryoid body homogeneity and cardiomyocyte differentiation from a novel V-96 plate aggregation system highlights interline variability. Stem Cells 25, 929-938 (2007). (Pubitemid 46572590)
84. Choi YY, Chung BG, Lee DH, Khademhosseini A, Kim JH, Lee SH. Controlled-size embryoid body formation in concave microwell arrays. Biomaterials 31, 4296-4303 (2010).
85. Xu F, Sridharan B, Wang S, Gurkan UA, Syverud B, Demirci U. Embryonic stem cell bioprinting for uniform and controlled size embryoid body formation. Biomicrofluidics 5, 22207 (2011).
86. Erceg S, Lainez S, Ronaghi M et al. Differentiation of human embryonic stem cells to regional specific neural precursors in chemically defined medium conditions. PLoS One 3, e2122 (2008).
87. Taylor CJ, Bolton EM, Pocock S, Sharples LD, Pedersen RA, Bradley JA. Banking on human embryonic stem cells: estimating the number of donor cell lines needed for HLA matching. Lancet 366, 2019-2025 (2005). (Pubitemid 41773377)
88. Lock LT, Tzanakakis ES. Expansion and differentiation of human embryonic stem cells to endoderm progeny in a microcarrier stirred-suspension culture. Tissue Eng. Part A 15, 2051-2063 (2009).
89. Lecina M, Ting S, Choo A, Reuveny S, Oh S. Scalable platform for human embryonic stem cell differentiation to cardiomyocytes in suspended microcarrier cultures. Tissue Eng. Part C Methods 16, 1609-1619 (2010).
90. Hentze H, Soong PL, Wang ST, Phillips BW, Putti TC, Dunn NR. Teratoma formation by human embryonic stem cells: evaluation of essential parameters for future safety studies. Stem Cell Res. 2, 198-210 (2009).
91. Fong CY, Gauthaman K, Bongso A. Teratomas from pluripotent stem cells: a clinical hurdle. J. Cell. Biochem. 111, 769-781 (2010).
92. Mummery CL. Cardiology: solace for the broken-hearted? Nature 433, 585-587 (2005).
93. Gersh BJ, Simari RD, Behfar A, Terzic CM, Terzic A. Cardiac cell repair therapy: a clinical perspective. Mayo Clin. Proc. 84, 876-892 (2009).
94. Gillard P, Keymeulen B, Mathieu C. Beta-cell transplantation in Type 1 diabetic patients: a work in progress to cure. Verh. K. Acad. Geneeskd. Belg. 72, 71-98 (2010).
95. Amit M, Chebath J, Margulets V et al. Suspension culture of undifferentiated human embryonic and induced pluripotent stem cells. Stem Cell Rev. 6, 248-259 (2010).
96. Wlaschin KF, Hu WS. Engineering cell metabolism for high-density cell culture via manipulation of sugar transport. J. Biotechnol. 131, 168-176 (2007). (Pubitemid 47187511)
97. Meuwly F, Weber U, Ziegler T et al. Conversion of a CHO cell culture process from perfusion to fed-batch technology without altering product quality. J. Biotechnol. 123, 106-116 (2006).
98. King JM, Titchener-Hooker NJ, Zhou Y. Ranking bioprocess variables using global sensitivity analysis: a case study in centrifugation. Bioprocess Biosyst. Eng. 30, 123-134 (2007).
99. Mason C, Dunnill P. Quantities of cells used for regenerative medicine and some implications for clinicians and bioprocessors. Regen. Med. 4, 153-157 (2009).
100. Nie Y, Bergendahl V, Hei DJ, Jones JM, Palecek SP. Scalable culture and cryopreservation of human embryonic stem cells on microcarriers. Biotechnol. Prog. 25, 20-31 (2009).
101. Krawetz R, Taiani JT, Lui S et al. Large scale expansion of pluripotent human embryonic stem cells in stirred-suspension bioreactors. Tissue Eng. Part C Methods 16, 573-582 (2010).
102. Xu C, Police S, Hassanipour M et al. Efficient generation and cryopreservation of cardiomyocytes derived from human embryonic stem cells. Regen. Med. 6, 53-66 (2011).