ABSTRACT
Microspheres with particle sizes of 60-300 μm have been successfully used as carriers of adherent cell culture. Cell culture system based on microspheres is called “microcarrier culture” due to the extremely important role of microspheres. Since Van Wezel first introduced diethyl amino ethyl (DEAE) dextran microspheres in the culture of adherent animal cells in 1967, microspheres have achieved many important applications in cell culture. The microcarrier technology has developed a number of biological products with vital practical and commercial value in the duration of forty years. These products include vaccines, enzymes, hormones, antibodies, interferons, and nucleic acids. Compared to traditional roller bottle cell culture, microcarrier culture combines the excellences of both the monolayer cell culture and suspension culture and provides many significant advantages (Handbooks from GE Healthcare, 2005). Some of these advantages are as follows: (i) The small spherical particles provide large surface-to-volume
ratio, which enhances production. For a given quantity of cells or products, microcarrier cultures require much less space than other types of monolayer cultures. Large numbers of cells
Weiqing Zhou, Guanghui Ma, and Zhiguo Su
can be cultured in small volumes (more than 1011 cells/L) and fewer culture vessels are required. This also greatly reduces the requirement of labor. (ii) Microcarrier culture require less culture media than other monolayer or suspension cultures. Superior yields as high as 100 times have been achieved in various cell systems including chicken fibroblasts (Giard et al., 1977; Mered et al., 1980), pig kidney cells (Meignier, 1979), fish cells (Nicholson, 1980), Chinese hamster ovary cells (Crespi & Thilly, 1981), human fibroblasts (Griffiths & Thornton, 1980), primary monkey kidney cells (van Wezel, 1972), and transformed mouse fibroblasts (Pharmacia Fine Chemicals, 1979). This reduced requirement for media significantly reduces the cost of production which is particularly high in the use of serum additives. (iii) The culture environment is homogeneous and has all the advantages of suspension culture. It is favorable for enlarging production and controlling culture conditions such as temperature, pH, CO2, and PO2. Monitoring and sampling microcarrier systems are simpler than any other existing technique for producing large numbers of adherent cells. Excellent control offers more convenience for process design and optimization. (iv) Microcarrier culture provides simplified, systematic, and automated procedures. Separation of cells from the culture medium is simple. As compared to culture in several hundred roller bottles, the risk of contamination is greatly reduced when producing cells in a single microcarrier culture bioreactor (Crespi & Thilly, 1981).
