Osmolality Effects on CHO Cell Growth, Cell Volume, Antibody Productivity and Glycosylation.
Osmolality Effects on CHO Cell Growth, Cell Volume, Antibody Productivity and Glycosylation.
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渗透压对CHO细胞生长、细胞体积、抗体产量和糖基化的影响。
DOI：
10.3390/ijms22073290
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发表时间：
2021-03-24
影响因子：
5.6
通讯作者：
Kontoravdi C
中科院分区：
文献类型：
--
作者：
Alhuthali S;Kotidis P;Kontoravdi C
中国仓鼠卵巢(CHO)细胞在补料分批培养过程中营养物质的添加和代谢产物的积累导致细胞外渗透压在培养后期增加。在此，我们探讨了渗透压对CHO细胞生长、特异性单抗(MAb)产量和糖基化的影响。虽然这两种方法都能提高特异性抗体的产量，但它们对细胞生长和抗体产生的影响不同。使用高达470mOsm kg−-1的氯化钠调节渗透压，对特异性抗体的产生和滴度有持续的积极影响。商业饲料的添加获得了不同的结果：特异性单抗产量增加，但细胞生长速度在高渗透压值下显著降低。结果表明，饲料C添加410mOsm kg−-1是获得显著高于对照组的mAb效价的唯一条件。此外，补充饲料C导致半乳糖化抗体结构显著减少。细胞体积与渗透压呈正相关；然而，如果不考虑细胞周期的变化，单靠渗透压不能解释观察到的细胞平均直径的变化。这些结果有助于描述渗透压对滴度的总体影响，并突出过度喂养对细胞生长的潜在负面影响。
The addition of nutrients and accumulation of metabolites in a fed-batch culture of Chinese hamster ovary (CHO) cells leads to an increase in extracellular osmolality in late stage culture. Herein, we explore the effect of osmolality on CHO cell growth, specific monoclonal antibody (mAb) productivity and glycosylation achieved with the addition of NaCl or the supplementation of a commercial feed. Although both methods lead to an increase in specific antibody productivity, they have different effects on cell growth and antibody production. Osmolality modulation using NaCl up to 470 mOsm kg−1 had a consistently positive effect on specific antibody productivity and titre. The addition of the commercial feed achieved variable results: specific mAb productivity was increased, yet cell growth rate was significantly compromised at high osmolality values. As a result, Feed C addition to 410 mOsm kg−1 was the only condition that achieved a significantly higher mAb titre compared to the control. Additionally, Feed C supplementation resulted in a significant reduction in galactosylated antibody structures. Cell volume was found to be positively correlated to osmolality; however, osmolality alone could not account for observed changes in average cell diameter without considering cell cycle variations. These results help delineate the overall effect of osmolality on titre and highlight the potentially negative effect of overfeeding on cell growth.
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影响因子：
3.5
作者：
Imai-Nishiya H;Mori K;Inoue M;Wakitani M;Iida S;Shitara K;Satoh M
通讯作者：
Satoh M
影响因子：
2.2
作者：
Hendrick, V;Winnepenninckx, P;Werenne, J
通讯作者：
Werenne, J
影响因子：
2.2
作者：
Konno, Yoshinobu;Kobayashi, Yuki;Hosoi, Shinji
通讯作者：
Hosoi, Shinji
影响因子：
3.8
作者：
Goey, Cher H.;Tsang, Joshua M. H.;Kontoravdi, Cleo
通讯作者：
Kontoravdi, Cleo
影响因子：
3.8
作者：
Kotidis, Pavlos;Jedrzejewski, Philip;Kontoravdi, Cleo
通讯作者：
Kontoravdi, Cleo