State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, 130 Meilong Road, Shanghai, 200237, China,
Adv Biochem Eng Biotechnol. 2009;113:177-215. doi: 10.1007/10_2008_19.
Some high value proteins and vaccines for medical and veterinary applications by animal cell culture have an increasing market in China. In order to meet the demands of large-scale productions of proteins and vaccines, animal cell culture technology has been widely developed. In general, an animal cell culture process can be divided into two stages in a batch culture. In cell growth stage a high specific growth rate is expected to achieve a high cell density. In production stage a high specific production rate is stressed for the expression and secretion of qualified protein or replication of virus. It is always critical to maintain high cell viability in fed-batch and perfusion cultures. More concern has been focused on two points by the researchers in China. First, the cell metabolism of substrates is analyzed and the accumulation of toxic by-products is decreased through regulating cell metabolism in the culture process. Second, some important factors effecting protein expression are understood at the molecular level and the production ability of protein is improved. In pace with the rapid development of large-scale cell culture for the production of vaccines, antibodies and other recombinant proteins in China, the medium design and process optimization based on cell metabolism regulation and protein expression improvement will play an important role. The chapter outlines the main advances in metabolic regulation of cell and expression improvement of protein in animal cell culture in recent years.
一些用于医学和兽医应用的高价值蛋白和疫苗，通过动物细胞培养在中国的市场需求不断增加。为了满足蛋白和疫苗的大规模生产需求，动物细胞培养技术得到了广泛的发展。一般来说，动物细胞培养过程可以在分批培养中分为两个阶段。在细胞生长阶段，期望实现高比生长速率以达到高细胞密度。在生产阶段，强调高比生产速率以实现合格蛋白的表达和分泌或病毒的复制。在补料分批培养和灌注培养中，保持高细胞活力始终是关键。中国的研究人员关注两个重点。首先，通过调节培养过程中的细胞代谢来分析基质的细胞代谢，并减少有毒副产物的积累。其次，在分子水平上了解影响蛋白表达的一些重要因素，并提高蛋白的生产能力。随着中国疫苗、抗体和其他重组蛋白的大规模细胞培养的快速发展，基于细胞代谢调控和蛋白表达改善的培养基设计和工艺优化将发挥重要作用。本章概述了近年来动物细胞培养中细胞代谢调控和蛋白表达改善的主要进展。
