Production of human-mouse chimeric antibody by high cell density perfusion culture

Takazawa, Yoshiharu; Tokashiki, Michiyuki

doi:10.1007/bf00386141

Cited by 8 publications

(3 citation statements)

References 20 publications

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“…For the separation of animal cells, sedimentation (Arai et al, 1993;Takazawa and Tokashiki, 1989;Tokashiki and Arai, 1989), centrifugation (Apelman, 1992;Jäger, 1992), acoustic filtration (Trampler et al, 1994), filtration with spin filters (Himmelfarb et al, 1969), and dynamic microfiltration techniques, like crossflow filtration (Maiorella et al, 1991;Mercille et al, 1994;van Reis et al, 1991) have been used. The main advantages and disadvantages of these different techniques can be summarized as follows:…”

Section: Animal Cell Separation Techniquesmentioning

confidence: 99%

Controlled shear filtration: A novel technique for animal cell separation

Vogel

Kroner

1999

Biotechnol. Bioeng.

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A novel rotary microfiltration technique specifically suited for the separation of animal cells has been developed. The concept allows the independent adjustment of wall shear stress, transmembrane pressure, and residence time, allowing straightforward optimization of the microfiltration process. By using a smooth, conically shaped rotor, it is possible to establish a controlled shear field in which animal cells experience a significant hydrodynamic lift away from the membrane surface. It is shown in preliminary experiments that shear‐induced cell‐rupture speeds up membrane clogging and that cell debris poses the most significant problem in harvesting of BHK cell cultures by dynamic microfiltration. However, a threshold value of shear stability exists which depends on the frequency of passing the shear field, the residence time in the shear field, as well as on cell status. By operating close to this threshold value, cell viability can be maintained while concentration polarization is efficiently minimized. By applying this concept, it is possible to attain flux rates several times higher compared to conventional crossflow filtration. Controlled shear filtration (CSF) can be used for batch harvesting as well as for cell retention in high cell density systems. In batch harvesting of hIL‐2 from rBHK cell culture, a constant flux rate of 290 L h−1 m−2 has been adjusted without indication of membrane clogging or fouling. © 1999 John Wiley & Sons, Inc. Biotechnol Bioeng 63: 663–674, 1999.

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Section: Animal Cell Separation Techniquesmentioning

confidence: 99%

Controlled shear filtration: A novel technique for animal cell separation

Vogel

Kroner

1999

Biotechnol. Bioeng.

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“…After an initial rapid growth period of perfusion culture, it is generally acknowledged that a second period of reduced growth occurs because of nutrient limitation at higher cell concentration. 20,28 In Experiment 11, it was clear that oxygen was the limiting factor in causing no further cell growth. However, it is not clear at present whether other nutrient limitations caused cell growth to stop in Experiment I. Amino acid analysis of the perfusion culture medium from Experiment I showed that amino acids were not limiting nutrients at the perfusion rate of 0.1 h-' and at the cell density of 3.4 X lo7 cells/mL (data not shown).…”

Section: Resultsmentioning

confidence: 98%

Monoclonal antibody productivity and the metabolic pattern of perfusion cultures under varying oxygen tensions

Shi

Ryu

Park

1993

Biotech & Bioengineering

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The metabolic pattern and cell culture kinetics of high-cell-density perfusion cultures were compared under two different oxygen transfer conditions: oxygen limiting and not limiting. When oxygen was a limiting factor during perfusion culture, both specific glucose uptake and lactate production rates increased, compared to non-oxygen-limited condition, by about 60% and 30%, respectively. The specific glutamine uptake rate under oxygen-limited conditions was almost 4.0 times higher than that under non-oxygen-limited conditions. The activity of lactate dehydrogenase (LDH) released into the medium by the dead cells can be used as an indicator for the metabolic and physiological conditions related to oxygen limitation. There was a 3.2 times higher specific rate of LDH activity released by dead cells in oxygen-limited cultures than those in non-oxygen-limited cultures. The specific production rate of monoclonal antibody was not significantly affected by the oxygen transfer conditions during the rapid cell growth period, but it rapidly increased toward the end of perfusion cultures. The higher perfusion rate may have limited further cell growth during high-cell-density perfusion culture, because cell damage was caused by the hydrodynamic shear within a hollow fiber microfiltration cartridge installed to withdraw the spent medium and the waste metabolites.

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“…Various techniques and devices to concentrate cells have been reported in the literature including sedimentation, 23 centrifugation, 24,25 and filtration. Various filtration have been used including spin filters, 26 vibrating and rotating disc filters, 27 cross-flow microfilter devices, 28 controlled shear filtration, 29 and tangential flow filtration 30 .…”

Section: Discussionmentioning

confidence: 99%

Novel technology to provide an enriched therapeutic cell concentrate from bone marrow aspirate

Ridgway¹,

Butcher²,

Chen³

et al. 2010

Biotechnology Progress

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Current strategies to repair fractures rely on orthopaedic surgeons harvesting bone from one area of the body, typically pelvis and transferring it to the fracture site. The amount of tissue available is therefore limited, requiring a second surgical procedure and often causing the patient long term pain. An alternative approach is utilise therapeutic cells contained within bone marrow aspirate during the primary procedure. The number of therapeutic cells within a fresh aspirate is insufficient to provide clinically acceptable bone healing in a timescale that is satisfactory to the surgeon and the patient. Therefore methods to efficiently concentrate bone marrow in the clinical setting are required. Centrifugation is the current method of choice but has limitations in that it requires large capital equipment, servicing and there are potential issues of tissue contamination. We have developed a novel, acoustically-assisted filtration device that addresses these limitations, delivering a concentrated bone marrow in a point of care, single use, fully disposable, compact device. An additional advantage is that the level of concentration required can be specified by the end user. The resulting bone marrow concentrate has been characterised in terms of cell number, viability and osteogenic potential using flow cytometry and alkaline phosphatase assay. When compared to recent clinical studies using bone marrow to repair non-union fractures, the findings from our work suggest that the bone marrow concentrate is likely to be highly therapeutic and clinically efficacious as a bone fracture repair strategy. A product concept for use in the clinical setting is presented.

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Production of human-mouse chimeric antibody by high cell density perfusion culture

Cited by 8 publications

References 20 publications

Controlled shear filtration: A novel technique for animal cell separation

Controlled shear filtration: A novel technique for animal cell separation

Monoclonal antibody productivity and the metabolic pattern of perfusion cultures under varying oxygen tensions

Novel technology to provide an enriched therapeutic cell concentrate from bone marrow aspirate

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