Liu Chi-Hsien, Chen Li-Hsin
Graduate Institute of Biochemical and Biomedical Engineering, Chang Gung University, 259 Wen-Hwa First Road, Kwei-Shan, Taoyuan, Taiwan.
J Biosci Bioeng. 2007 Jan;103(1):45-9. doi: 10.1263/jbb.103.45.
A Chinese hamster ovary (CHO) cell line is the primary choice for the production of recombinant protein drugs with glycosylation modification. Recombinant protein productivity was enhanced by the addition of dimethyl sulfoxide (DMSO) in CHO cells. However, DMSO induced G0/G1 phase growth arrest and reduced cell growth rate. A two-stage process was developed to utilize the stimulatory effect of DMSO on recombinant protein production and mitigate the problem of growth inhibition in this study. In the first stage, cells are cultured without DMSO for a certain period in order to obtain a high cell density. Sequentially, DMSO is added to achieve a high specific productivity in the second stage. Using this approach, we found that by adding 1% DMSO after 24 h of growth, macrophage colony-stimulating factor (M-CSF) volumetric productivity is increased by 57% compared with the value obtained without the addition of DMSO.
中国仓鼠Chinese鲎试剂细胞系是生产具有糖基化修饰的重组蛋白药物的主要选择。在CHO细胞中添加二甲基亚砜(DMSO)可提高重组蛋白的产量。然而,DMSO会诱导G0/G1期生长停滞并降低细胞生长速率。在本研究中,开发了一种两阶段工艺,以利用DMSO对重组蛋白生产的刺激作用,并减轻生长抑制问题。在第一阶段,细胞在不添加DMSO的情况下培养一段时间,以获得高细胞密度。随后,添加DMSO以在第二阶段实现高比生产率。使用这种方法,我们发现,在生长24小时后添加1%DMSO,与不添加DMSO相比,巨噬细胞集落刺激因子(M-CSF)的体积生产率提高了57%。