Abstract
In this chapter, scale-up is described in a laboratory context (10–20 L), but the principles and techniques employed have been successfully adapted so that cells are now grown industrially in unit volumes of up to 10,000 L for vaccine, interferon, and monoclonal antibody production. The need to scale-up cell cultures has been expanded from the historical requirement for vaccine manufacture to include not only interferon and antibodies, but many important medical products such as tissue plasminogen activator, erythropoitin, and a range of hormones and blood factors. The low productivity of animal cells, resulting from their slow growth rate and low expression of product, plus the complexity of the growth conditions and media, led to attempts to use recombinant bacteria to express mammalian cell and virus proteins. However, this has proven unsuitable for many products, mainly because of incomplete expression and contamination with bacterial toxins, and more importance is now being put on expression of recombinant proteins from mammalian cells. This has allowed the use of faster growing and less fastidious cell lines, such as CHO, and amplification of product expression by multiple copies of the gene.
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References
Spier, R. E. and Griffiths, J. B. (1983) An examination of the data and concepts germane to the oxygenation of cultured animal cells. Develop. Biol. Stand. 55, 81–92.
Griffiths, J. B. (1986) Scaling-up of animal cells, in Animal Cell Culture: A Practical Approach (Freshney, I., ed.), IRL Press, Oxford, UK, pp. 33–70.
Griffiths, J. B., Cameron, D. R., and Looby, D. (1987) A comparison of unit process systems for anchorage dependent cells. Develop. Biol. Stand. 66, 331–338.
Griffiths, J. B. (1986) Can cell culture medium costs be reduced? Strategies and possibilities. Trends Biotechnol. 4, 268–272.
Whiteside, J. P. and Spier, R. E. (1981) The scale-up from 0.1 to 100 liter of a unit process system based on 3 mm diameter glass spheres for the production of four strains of FMDV from BHK monolayer cells. Biotechnol. Bioeng. 23, 551–565.
Mignot, G., Faure, T., Ganne, V., Arbeille, B., Pavirani, A., and Romet-Lemonne, J. L. (1990) Production of recombinant Von Willebrand factor by CHO cells cultured in macroporous microcarriers. Cytotechnology 4, 163–171.
Looby, D., Racher, A. J., and Griffiths, J. B. (1995) Evaluation of a porous silicone carrier (ImmobaSil G) for animal cell culture, in Animal Cell Technology—Developments Towards the 21st Century. (Beuvery, E. C., Griffiths, J. B., and Zeijlemaker, W. P., eds.), Kluwer Academic Publishers, Dordrecht, pp. 783–786.
Looby, D. and Griffiths, J. B. (1988) Fixed bed porous glass sphere (porosphere) bioreactors for animal cells. Cytotechnology 1, 339–346.
Looby, D. and Griffiths, J. B. (1989) Immobilisation of animal cells in fixed and fluidised porous glass sphere reactors, in Advances in Animal Cell Biology and Technology for Bioprocessors (Spier, R. E., Griffiths, J. B., Stephenne, J., and Crooy, P. J., eds.), Butterworths, Guildford, UK, pp. 336–344.
Looby, D., Rather, A. J., Griffiths, J. B., and Dowsett, A. B. (1990) The immobilisation of animal cells in fixed and fluidised porous glass sphere reactors, in Physiology of Immobilised Cells (deBont, J. A. M., Visser, J., Mattiasson, B., and Tramper, J., eds.), Elsevier Science Publishers BV, Amsterdam, pp. 225–264.
Ray, N. G., Tung, A. S., Hayman, E. G., Vournakis, J. N., and Runstadler, P. W. Jr. (1990) Continuous cell culture in fluidised bed reactors: cultivation of hybridomas and recombinant CHO cells immobilised in collagen microspheres. Ann. NY Acad. Sci. Biochem. Eng. VI 589, 443–457.
Renter, M., Hohenwarter, O., Gaida, T., Zach, N., Schmatz, C., Bluml, G., Weigang, F., Nilsson, K., and Katinger, H. (1990) The use of macroporous carriers for the cultivation of mammalian cells in fluidised bed reactors. Cytotechnology 3, 271–277.
Reiter, M., Bluml, G., Gaida, T., Zach, N., Unterluggaaer, F., Dublhoff-Dier, M., Noe, R., PlacL, R., Huss, S., and Katinger, H. (1991) Modular integrated fluidised bed bioreactor technology. Biotechnology 9, 1100–1102.
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© 1997 Humana Press Inc., Totowa, NJ
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Griffiths, B., Looby, D. (1997). Scale-Up of Suspension and Anchorage-Dependent Animal Cells. In: Pollard, J.W., Walker, J.M. (eds) Basic Cell Culture Protocols. Methods in Molecular Biology™, vol 75. Humana Press, Totowa, NJ. https://doi.org/10.1385/0-89603-441-0:59
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DOI: https://doi.org/10.1385/0-89603-441-0:59
Publisher Name: Humana Press, Totowa, NJ
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