Effects of copper on CHO cells: Cellular requirements and product quality considerations
Effects of copper on CHO cells: Cellular requirements and product quality considerations
复制标题
铜对 CHO 细胞的影响：细胞要求和产品质量考虑因素
DOI：
--
复制
发表时间：
2015
期刊：
影响因子：
--
通讯作者：
J. Joly
中科院分区：
文献类型：
--
作者：
Inn H. Yuk;S. Russell;Yun Tang;W. Hsu;J. B. Mauger;Rigzen P. S. Aulakh;Jun Luo;M. Gawlitzek;J. Joly
最近的报告强调了铜对乳酸代谢的影响：具有较高初始铜水平的CHO细胞培养转变为净乳酸消耗，并产生较低的最终乳酸和较高的效价。这些研究调查了铜对代谢物和转录物的影响，但没有详细测量细胞培养性能和产品质量与铜浓度的依赖关系。为了更彻底地描绘这些依赖关系，我们探索了不同铜处理对四个重组CHO细胞系的影响。在第一个细胞系中，当细胞外铜保持在检测下限(LOD)以上时，无论铜水平如何，培养物转向净乳酸消耗并产生类似的表现；当细胞外铜降至LOD值以下(∼13 NM)时，培养物未能转移到净乳酸消耗，并产生显著更低的产品效价。在四种细胞系中，生长和消耗乳酸的能力似乎取决于最低水平的铜的存在，超过这一水平，培养性能就不会进一步提高。虽然这一最低细胞铜需要量不能直接量化，但我们通过应用几个假设估计了它对第一个细胞系的可能范围。即使不同的铜浓度不影响细胞培养性能，它们也会影响产品质量：较高的初始铜浓度会增加重组IgG1产品中的基本变异体。因此，在优化化学定义的介质时，重要的是选择足够的铜浓度并实现所需的产品质量属性。©2014美国化学工程师学会生物技术。程序，31：226-238,2015
Recent reports highlight the impact of copper on lactate metabolism: CHO cell cultures with higher initial copper levels shift to net lactate consumption and yield lower final lactate and higher titers. These studies investigated the effects of copper on metabolite and transcript profiles, but did not measure in detail the dependences of cell culture performance and product quality on copper concentrations. To more thoroughly map these dependences, we explored the effects of various copper treatments on four recombinant CHO cell lines. In the first cell line, when extracellular copper remained above the limit of detection (LOD), cultures shifted to net lactate consumption and yielded comparable performances irrespective of the differences in copper levels; when extracellular copper dropped below LOD (∼13 nM), cultures failed to shift to net lactate consumption, and yielded significantly lower product titers. Across the four cell lines, the ability to grow and consume lactate seemed to depend on the presence of a minimum level of copper, beyond which there were no further gains in culture performance. Although this minimum cellular copper requirement could not be directly quantified, we estimated its probable range for the first cell line by applying several assumptions. Even when different copper concentrations did not affect cell culture performance, they affected product quality profiles: higher initial copper concentrations increased the basic variants in the recombinant IgG1 products. Therefore, in optimizing chemically defined media, it is important to select a copper concentration that is adequate and achieves desired product quality attributes. © 2014 American Institute of Chemical Engineers Biotechnol. Prog., 31:226–238, 2015
影响因子：
4.2
作者：
PROHASKA, JR
通讯作者：
PROHASKA, JR