33: 300–305.Ĭlark JM and Hirtenstein MD (1981) Optimizing culture conditions for the production of animal cells in microcarrier culture. 32: 1001–1014.Ĭherry RS and Papoutsakis ET (1989) Modeling of contact-inhibited animal cell growth on flat surfaces and spheres. 1: 29–41.Ĭherry RS and Papoutsakis ET (1988) Physical mechanisms of cell damage in microcarrier cell culture bioreactors. 260: 320–333.Ĭherry RS and Papoutsakis ET (1986) Hydrodynamic effects on cells in agitated tissue culture reactors. 6: 224–230.Ĭhapman AE and Calhoun JC (1988) Effects of glucose starvation and puromycin treatment on lipid-linked oligosaccharide precursors and biosynthetic enzymes in Chinese hamster ovary cells in vivo and in vitro. 6: 153–166.īliem R and Katinger H (1988) Scale-up engineering in animal cell technology: Part II. Bio/Technology 8: 54–58.īichay JT, Adams EG, Inch RW, Brewer JE and Bhuyan BK (1990) HPLC and flow cytometric analyses of uptake of adriamycin and menogaril by monolayers and multicell spheroids.
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There was also a decrease in bridging in cultures supplemented with either 1% calf serum or 1% dimethyl sulfoxide/1% calf serum compared to serum-free cultures.Īvgerinos GC, Drapeau D, Socolow JS, Mao J, Hsiao K and Broeze RJ (1990) Spin filter perfusion system for high density cell culture: production of recombinant urinary type plasminogen activator in CHO cells. Thus, maintaining confluent microcarriers in medium supplemented with 1% dimethyl sulfoxide and 1% calf serum resulted in microcarriers that appeared similar to monolayer cultures. The development of cellular overgrowth was inhibited by dimethyl sulfoxide. The development of bare spots was inhibited when confluent microcarriers were maintained in medium supplemented with 1% serum. This ultimately led to poor surface coverage as bare spots developed on the microcarrier away from the areas of dense cellular overgrowth. To replace cells that were continuously sheared from the microcarriers, cell growth occurred preferentially in areas of overgrowth after confluent microcarriers were maintained in a serum-free medium. Dense masses of cellular overgrowth formed inside bridges connecting the microcarriers and in clumps that protruded off the microcarrier surface. The level of microcarrier aggregation decreased with increasing agitation intensity.
Microcarrier aggregation by cellular bridge formation was found to occur only during periods of rapid cell growth. We have investigated conditions that inhibit the tendency of CHO K1 cells to form cellular bridges between microcarriers and dense clumps of cellular overgrowth in microcarrier cultures.
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