High cell density perfusion culture of mouse-human hybridomas

Takazawa, Yoshiharu; Tokashiki, Michiyuki

doi:10.1007/bf00184974

Cited by 30 publications

(6 citation statements)

References 14 publications

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“…Perfusion feeding culture strategies, used to obtain very high cell densities, are also well developed for stirred vessel culture systems and are readily implementable (Lang and Schuerch, 1998;Takazawa and Tokashiki, 1989).…”

Section: Introductionmentioning

confidence: 99%

Culture of human T cells in stirred bioreactors for cellular immunotherapy applications: Shear, proliferation, and the IL-2 receptor

Carswell

Papoutsakis

2000

Biotechnol. Bioeng.

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Section: Introductionmentioning

confidence: 99%

Culture of human T cells in stirred bioreactors for cellular immunotherapy applications: Shear, proliferation, and the IL-2 receptor

Carswell

Papoutsakis

2000

Biotechnol. Bioeng.

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“…Perfusion culture methods have become a method of choice for high-density ~u l t u r e s , ' ,~, '~,~~,~~ and necessarily, the application of serum-free media has been successful in many cases. 19,23,24 * To whom all correspondence should be addressed. sity, 253 Yonghyun-Dong, Nam-Ku, lncheon 402-751, Korea.…”

Section: Ntro D U Ctlo Nmentioning

confidence: 99%

Repeated fed‐batch culture of hybridoma cells in nutrient‐fortified high‐density medium

Jo¹,

Park²,

Kim³

et al. 1993

Biotech & Bioengineering

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Long-term high-density cultivation of the hybridoma 2c3.1 was successfully carried out in a repeated fed-batch mode using high-density media that were constructed to meet in vitro cell growth limitations. The high-density culture was possible in a range of 0.5 approximately 1.0 x 10(7) cells/mL in MBRI 40-02 medium for over 2500 h by the repeated supplementation of the most fortified medium, MBRI 40-03, and consequently, distinct enhancement of MAb production was achieved. MAb concentrations were maintained around 1 g/L for about 1000 h of the process and the maximum MAb concentration was around 1.56 g/L. The result supported strongly the fact that the nutritional fortification was the most critical factor for high-density cell culture in vitro. The mean chromosome number of the hybridoma 2c3.1 was maintained stably for about 1500 h, whereas gradual loss of the MAb activity was apparent during the long-term cultivation.

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“…Continuous cultures with cell retention or recy-cle are increasingly being used to increase the cell concentration and the productivity for a given reactor volume (Kitano, Shintani et al, 1986;Takazawa and Tokashiki, 1989;Batt, Davis et al, 1990;Comer, Kearns et al, 1990;Seamans and Hu, 1990;Tokashiki, Arai et al, 1990;de la Broise, Noiseux et al, 1991;Hu and Peshwa, 1991;Hu and Piret, 1992;Kyung, Peshwa et al, 1994;Laporte, Shevitz et al, 1995;Takamatsu, Hamamoto et al, 1996). These cultures, often referred to as perfusion cultures, can lead to 5-10 fold increase in cell concentration and product throughput over conventional batch and continuous cultures.…”

Section: Introductionmentioning

confidence: 99%

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et al. 1999

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Continuous culture is frequently used in the cultivation of mammalian cells for the manufacturing of recombinant protein pharmaceuticals. In such operations a large volume of medium is turned over each day, especially in the case where cell recycle, or perfusion cultivation, is practiced. In principle, the volumetric throughput of medium can be reduced by using a more concentrated feed while maintaining the same nutrient provision rate. Overall, the medium components are divided into two categories: 'consumable nutrients' and 'unconsumable inorganic bulk salts'. In such fortified medium, the concentrations of consumable nutrients, but not bulk salts, are increased. With a stoichiometrically-balanced medium, the large amount of nutrients fed into the culture is largely consumed by cells to give rise to residual concentrations of these nutrients in their optimal range. However, unless care is taken to initiate the continuous culture, overshoot of nutrients may occur during the transient period. The high nutrient concentration during overshoot may be inhibitory by itself, or the resulting high osmolality may retard the growth. Using a mathematical model that incorporates the growth inhibitory effect of high osmolality we demonstrate such a potentially catastrophic effect of nutrient and osmolality overshoot by simulation. To avoid overshoot a controlled nutrient feeding scheme should be devised at the initiation of continuous culture.

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High cell density perfusion culture of mouse-human hybridomas

Cited by 30 publications

References 14 publications

Culture of human T cells in stirred bioreactors for cellular immunotherapy applications: Shear, proliferation, and the IL-2 receptor

Culture of human T cells in stirred bioreactors for cellular immunotherapy applications: Shear, proliferation, and the IL-2 receptor

Repeated fed‐batch culture of hybridoma cells in nutrient‐fortified high‐density medium

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