Jayme D W, Blackman K E
Adv Biotechnol Processes. 1985;5:1-30.
In this brief review, we have illustrated the historical development of the growth media commonly employed for the propagation of cultured mammalian cells. While substantial progress has been achieved, the field may best be described as conservative and pragmatic. To date, the function of many components of the growth medium essential for cellular proliferation and biological production has not been precisely defined at the molecular level. Thus, for most large-scale biological production requirements, as well as for routine cell culture and bench-scale pilot development, the traditional enriched culture medium supplemented with fetal bovine serum represents the most convenient culture system. Many cell types may be more economically grown without reduction in biological yield by substituting alternative mammalian sera. Where reduction of total protein or greater definition of growth medium components outweighs the use of more universally applicable culture media, substitution of serum-free, customized formulations of highly enriched growth medium plus defined growth factors may be of significant utility. Optimization of mammalian cell culture media for large-scale biological production should include the following: An initial time investment to optimize the cell culture medium by enriching intermediary metabolite composition (rather than expecting serum or additional growth factors to perform nutritional functions) may result in higher productivity and reduced cost. When screening potential growth media for biological production applications, proliferative rate should not be the sole criterion for performance. Although rapid, logarithmic growth is advantageous to establish large-scale cultures, the maximal cell density and duration of the viable, productive period must also be weighed. Many cell types generate the highest titers of biological product either at stationary phase or under mildly stressful ("controlled death") conditions suboptimal for cellular replication. Thus, the ultimate determinant of growth medium efficacy is neither the degree of definition of medium composition nor the cellular proliferative rate, but the ability to support synthesis of substantial titers of the desired product at reasonably high purity.
在这篇简短的综述中，我们阐述了常用于培养哺乳动物细胞的生长培养基的历史发展。尽管已取得了显著进展，但该领域最好被描述为保守且务实的。迄今为止，细胞增殖和生物制品生产所必需的生长培养基中许多成分的功能，在分子水平上尚未得到精确界定。因此，对于大多数大规模生物制品生产需求以及常规细胞培养和实验室规模的中试开发而言，添加胎牛血清的传统富集培养基是最便捷的培养系统。通过替代其他哺乳动物血清，许多细胞类型可以更经济地生长，而不会降低生物产量。当降低总蛋白含量或更明确生长培养基成分比使用更通用的培养基更为重要时，用无血清、高度富集的生长培养基定制配方加特定生长因子进行替代可能具有显著效用。用于大规模生物制品生产的哺乳动物细胞培养基的优化应包括以下方面：最初投入时间通过富集中间代谢物组成来优化细胞培养基（而非期望血清或其他生长因子发挥营养功能），这可能会提高生产力并降低成本。在筛选用于生物制品生产应用的潜在生长培养基时，增殖速率不应是性能的唯一标准。尽管快速的对数生长有利于建立大规模培养物，但还必须权衡最大细胞密度和存活、生产期的持续时间。许多细胞类型在稳定期或对细胞复制而言并非最适宜的轻度应激（“可控死亡”）条件下产生最高滴度的生物制品。因此，生长培养基功效的最终决定因素既不是培养基成分的明确程度，也不是细胞增殖速率，而是以合理高纯度支持合成大量所需产物的能力。
