Birch J R, Arathoon R
Celltech Ltd., Slough, England.
Bioprocess Technol. 1990;10:251-70.
Mammalian cell suspension culture systems are being used increasingly in the biotechnology industry. This is due to their many advantages including simplicity and homogeneity of culture. Suspension systems are very adaptable (e.g., for microcarrier, microencapsulation, or other methods of culture). Their engineering is thoroughly understood and standardized at large scale, and automation and cleaning procedures are well established. Suspension systems offer the possibility of quick implementation of production protocols due to their ability to be scaled easily once the basic culture parameters are understood. The only main disadvantage of the suspension culture systems to date is their inapplicability for the production of human vaccines from either primary cell lines or from normal human diploid cell lines (Hayflick et al., 1987 and references therein). One of the great advantages of suspension culture is the opportunity it provides to study interactions of metabolic and production phenomena in chemostat or turbidostat steady-state systems. Furthermore, in suspension culture systems from which cell number and cell mass measurements are easy to obtain, rigorous and quantitative estimations of the effects of growth conditions or perturbations of metabolic homeostasis can be made. Such studies can speed up the development of optimal processes. With our increasing understanding of factors influencing expression in mammalian cells (Cohen and Levinson, 1988; Santoro et al., 1988) and the direct application of new methods in suspension culture (Rhodes and Birch, 1988), its usefulness and importance is likely to increase in the future. In this chapter, we have described some of the potential uses of the various suspension culture systems and have covered most of the established technology and literature. Due to the rapid developments and needs in the biotechnology industry and the versatility of suspension culture systems, it is probable that many more variations on this theme will evolve in the near future at both the pilot and production scales.
哺乳动物细胞悬浮培养系统在生物技术产业中的应用越来越广泛。这是因为它们具有许多优点,包括培养的简单性和均一性。悬浮系统具有很强的适应性(例如,适用于微载体、微囊化或其他培养方法)。其工程原理已被充分理解并在大规模生产中实现了标准化,自动化和清洗程序也已成熟。一旦掌握了基本的培养参数,悬浮系统就能够很容易地进行扩大培养,从而具备快速实施生产方案的可能性。迄今为止,悬浮培养系统的唯一主要缺点是它们不适用于从原代细胞系或正常人二倍体细胞系生产人类疫苗(Hayflick等人,1987年及其中的参考文献)。悬浮培养的一大优点是它为研究恒化器或恒浊器稳态系统中的代谢和生产现象之间的相互作用提供了机会。此外,在易于获得细胞数量和细胞质量测量值的悬浮培养系统中,可以对生长条件或代谢稳态扰动的影响进行严格和定量的评估。此类研究可以加速优化工艺的开发。随着我们对影响哺乳动物细胞表达的因素的理解不断加深(Cohen和Levinson,1988年;Santoro等人,1988年)以及新方法在悬浮培养中的直接应用(Rhodes和Birch,1988年),其在未来的实用性和重要性可能会增加。在本章中,我们描述了各种悬浮培养系统的一些潜在用途,并涵盖了大多数已有的技术和文献。由于生物技术产业的快速发展和需求以及悬浮培养系统的多功能性,在不久的将来,无论是中试规模还是生产规模,围绕这一主题可能会出现更多的变化。