Abstract
Cell culture techniques have become vital to the study of animal cell structure, function, and differentiation and for the production of many important biological materials such as vaccines, enzymes, hormones, antibodies, interferons, and nucleic acids. Microcarrier culture introduces new possibilities and, for the first time, allows practical high-yield culture of anchorage-dependent cells (1). In microcarrier culture, cells grow as monolayers on the surface of small spheres or as multilayers in the pores of macroporous structures that are usually suspended in culture medium by gentle stirring. By using microcarriers in simple suspension culture, fluidized or packed bed systems, yields of up to 200 million cells per milliliter are possible.
The following microcarrier examples described in the procedures represent the major types: (1) Cytodex™ (GE Healthcare) represents spherical microcarriers for anchoragedependent cells, mainly for vaccine production; (2) Cytopore™ (GE Healthcare) represents macroporous microcarriers for anchorage and suspension cells in stirred tank reactors, mainly for r-protein production and monoclonal antobodies; (3) Cytoline™ (GE Healthcare) represents weighed macroporous microcarriers for fluidized bed applications.
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References
van Wezel, A.L. (1967) Growth of cell strains and primary cells on microcarriers in homogeneous culture. Nature 216, 64–65.
Nilsson, K., Buzsaky, F., and Mosbach, K. (1986) Growth of anchorage dependent cells on macroporous microcarrier. Biol. Technol. 4, 989–990.
Young, M. W. and Dean, R. C. (1987) Optimization of mammalian-cell bioreactors. Biotechnology 5, 835–837.
Swamy, J. (2003) Genzyme. The development of long term, microcarrier-based perfusion process for the production of recombinant proteins. IBC Conference, Cell Culture and Upstream Processing, San Diego.
Müller, D., Unterluggauer, F., Kreismayr, G., et al. (1999) Continuous perfused Fluidized bed technology, Increased productivities and product concentration. Proceedings of the 16th ESACT Meeting: Animal Cell Technology: Products from Cells, Cells as Products (Bernard, Griffiths, Noe, Wurm, eds.), pp. 319–321.
Reiter, M. (2004) Vaccine production with a contiuous perfusion system. Cell culture and upstream processing conference, Sept 13–14, Berlin, Germany.
Kasche, V., Probst, K., and Maass, J. (1980) The DNA and RNA content of crude and crystalline trypsin used to trypsinize animal cell cultures: kinetics of trypsinization. Eur. J. Cell Biol. 22, 388.
Dehm, P. and Prockop, D. I. (1971) Synthesis and extrusion of collagen by freshly isolated cells from chick embryo tendon. Biochim. Biophys. Acta 250, 358–369.
Griffiths, B., Thornton, B., and McEntee, I. (1980) Production of herpes viruses in microcarrier cultures of human diploid and primary chick fibroblast cells. Eur. J. Cell Biol. 22, 606.
Meignier, B. (1979) Cell culture on beads used for the industrial production of foot-and-mouth disease virus. Dev. Biol. Standard 42, 141–145.
Meignier, B., Mougeot, H., and Favre, H. (1980) Foot and mouth disease virus production on microcarrier-grown cells. Dev. Biol. Standard 46, 249–256.
BüimL, G., Reiter, M., Zach, N., et al. (1998) Fluidized bed technology: Influence of fluidization velocity on nutrient consumption and product expression. Proceedings of the 15th ESACT Meeting: New Developments and New Applications in Animal Cell Technology), pp. 385–387.
vanWezel, A. L. (1985) Monolayer growth systems: homogeneous unit processes, in Animal Cell Biotechnology (Spier, R. E. and Griffiths, J. B., eds.), Academic Press Inc., London, pp 266–281.
Mosmann, T. (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J. Immunol. Methods 65, 55.
Capiaumont, J., Legrand, C., Gelot, M. A., Straczek, J., Belleville, F., and Nabet, P. (1993) Search for cell proliferation markers suitable for cell count in continuous immobilized cell bioreactors. J. Biotechnol. 31, 147–160.
Sanford, K. K., Earle, W. R., Evans, V. J., et al. (1951) The measurement of proliferation in tissue cultures by enumeration of cell nuclei. J. Nat. Cancer Inst. 11, 773–795.
van Wezel, A. L., Kruse, P. F., and Patterson, M. K., eds. (1973) Microcarrier cultures of animal cells, in Tissue Culture: Methods and Applications, Academic Press, New York, pp. 372–377.
Patterson, M. K. (1979) Measurement of growth and viability of cells in culture. Methods Enzymol. 58, 141–152.
Horng, C.-B. and McLimans, W. (1975) Primary suspension culture of calf anterior pituiary cells on a microcarrier surface. Biotechnol. Bioeng. 17, 713–732.
Manousos, M., Ahmed, M., Torchio, C., et al. (1980) Feasibility studies of oncornavirus production in microcarrier cultures. In Vitro 15, 507–515.
Pawlowski, K. R., Loyd, R., and Przybylski, R. (1979) Skeletal muscle development in culture on beaded microcarriers, Cytodex 1. J. Cell Biol. 83, 115 A.
Prokop, A. and Rosenberg, M. Z. (1989) Bioreactor for mammalian cell culture. Adv. Biochem. Eng. 39, 29.
Anghileri, L. J. and Dermietzel, P. (1976) Cell coat in tumour cells—effects of trypsin and EDTA; a biochemical and morphological study. Oncology 33, 11–23.
Lai, C., Hopwood, L. E., and Swartz, H. M. (1980) ESR studies on membrane fluidity of Chinese hamster ovary cells groown on microcarriers and in suspension. Exp. Cell Res. 130, 437–442.
Kamiya, K., Yanagida, K., and Shirokaze, J. (1995) Subculture method for large scale cell culture using macroporous microcarrier. In: Beuvery, Griffiths, Zeiglemaker (eds.) Developments toward the 21st Century. Kluwer Academic Publisher, Dordrecht, pp. 759–763.
Dürrschmid, M., Landauer, K., Simic, G., BlümL, G., and Doblhoff-Dier, O. (2003) Scaleable inoculation strategies for microcarrier-based animal cell bioprocesses. Biotechnol. Bioeng. 83, 681–686.
Landauer, K., Dürrschmid, M., Klug, H., Wiederkum, S., BlümL, G. and Doblhoff-Dier, O. (2002) Detachment factors for enhanced carrier to carrier transfer of CHO cell lines on macroporous microcarriers. Cytotechnology 39, 37–45.
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© 2007 Humana Press Inc., Totowa, NJ
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Blüml, G. (2007). Microcarrier Cell Culture Technology. In: Pörtner, R. (eds) Animal Cell Biotechnology. Methods in Biotechnology, vol 24. Humana Press. https://doi.org/10.1007/978-1-59745-399-8_5
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DOI: https://doi.org/10.1007/978-1-59745-399-8_5
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