Process Engineering Study on Specific Environmental Factors of Mammalian Cell Culture
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概要
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The effects and control of specific environmental factors on mammalian cell culture and control of their factors were investigated. (i) After studying the basal environmental factors such as temperature, pH, and dissolved oxygen (DO) and developing a low-serum medium, a novel aeration strategy of supplying dissolved oxygen without cell damage in a large scale culture, which involves the usage of an air-spray system and pressurization, was proposed. A practical method for the on-line measurement of respiration rate as an index of the physiological state of cells was developed and applied to a shift of control mode of a microcarrier culture of human embryo lung cells producing the tissue plasminogen activator (tPA). (ii) A novel carrier of chemically modified starch particles was developed with the aim of convenient cell separation during medium change in suspension culture of tPA-producing Chinese hamster ovary (CHO) cells. Another cell separation method employing a low centrifugal force was effective in maintaining the specific tPA production rate at high levels during suspension culture. (iii) The change in the morphology of adhesive cells and the increase in energy metabolism, which major substrate shifted from glucose to glutamine, were considered to correlate with the increase in the specific production rate of proteins under a high osmotic pressure. The gradual increase and cyclic change of osmotic pressure during culture were found to increase the production of proteins such as monoclonal antibody (MAb) and tPA. Static pressurization at 0.9 MPa increased MAb production by hybridoma cells. These results may be useful to solve specific problems in industrial processes of mammalian cell culture.
- 公益社団法人日本生物工学会の論文
- 2002-02-25
著者
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Takagi Mutsumi
International Center For Biotechnology Osaka University
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Takagi Mutsumi
Internatioal Center For Biotechnology Osaka University
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