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Enhancement of tPA production under hyperoxic conditions by BHK cells in serum-free and serum-containing cultures
Institution:1. Department of Biotechnology, Faculty of Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-01, Japan;2. Eisai Co. Ltd., Tsukuba Research Laboratories, 1-3, Tokodai 5-chome, Tsukuba-shi, Ibaraki 300-26, Japan;1. National Institute of Materials Physics, Atomistilor Str. 405A, 077125 Magurele, Romania;2. Institute of Cellular Biology and Pathology ‘Nicolae Simionescu’, Biopathology and Therapy of Inflammation, Bucharest, Romania;1. Upstream Development, Novo Nordisk A/S, Brennum Park 25K, Hillerød, Denmark;2. Cultivation Pilot Plants, Novo Nordisk A/S, Brudelysvej 22, Bagsværd, Denmark;1. Center for Microflows and Nanoflows, Harbin Institute of Technology (Shenzhen), Shenzhen 518000, China;2. Shanghai Key Laboratory of Functional Materials Chemistry, School of Chemistry and Molecular Engineering, East China University of Science and Technology, Shanghai 200237, China;3. State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China;4. Shanghai Ji Ai Genetics & IVF Institute, Obstetrics & Gynecology Hospital, Fudan University, Shanghai 200011, China;5. Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, China;6. School of Science, RMIT University, Melbourne, VIC 3001, Australia
Abstract:Effects of a wide range of dissolved oxygen concentration (DO, 0.5–28 mg/l) on anchorage-dependent BHK cell growth, metabolism and tPA production were examined with both serum-containing and serum-free media. In the range of DO from 0.5 to 5 mg/l, tPA production increased with an increase in DO in both media. Cell growth was higher at 5 mg/l DO than that at 0.5 or 2 mg/l DO in serum-containing medium, but it did not vary in serum-free medium in this DO range. Further investigation under hyperoxic conditions (DO > 6.8 mg/l) revealed that specific rates of tPA production were enhanced by 2-fold in serum-containing and 1.7-fold in serum-free media, although cell growth depressed above 5 mg/l of DO. Slight increases in specific rates of lactate accumulation and glucose consumption were observed in both media under hyperoxic conditions. In serum-free medium, cells were found to be less tolerant to hyperoxic conditions than those in serum-containing medium. A DO shift-up with shifting time of 4 h in serum-containing medium was found to influence significantly both cell growth and tPA production.
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