Laboratory for Product and Process Development, National Institute of Public Health and Environmental Protection (RIVM), P.O. Box 1, 3720 BA, Bilthoven, The Netherlands.
Cytotechnology. 1995 Jan;18(1-2):51-6. doi: 10.1007/BF00744319.
Only a decade after Van Wezel introduced the first product made in microcarrier cultures on industrial scale at economically acceptable costs, namely Inactivated Polio Vaccine (IPV), interest was taken in this revolutionary type of cell growth system. The basic idea was to develop a culture system with equal potentials for control of environmental culture conditions and scaling up as the systems used in industrial microbiology. Although initially only positively-charged beads were used it soon became clear that negatively-charged or amphoteric materials such as proteins or amino acids polymerized to the surface were equally useful. Eventually numerous different types of microcarrier were developed. The second generation of microcarriers consisted of macroporous beads providing increased surface area for cell attachment and growth by external and interior space. Such microcarriers offer great potential for high cell densities and enhanced productivity for certain production systems, especially recombinant CHO-cells. These carriers, which not only provide possibilities for anchorage-dependent cells but also for cells growing suspension, can be used in homogeneous bioreactors as well as in fluidized or fixed-bed systems. Despite considerable in vestments and research on the development and improvement of microcarriers one question is still open: is microcarrier technology still in its infancy or is it full-grown and is the basic idea relized? In this paper a general overview will be given of the present state of microcarrier technology and also of its perspectives.
在范韦泽(Van Wezel)引入第一个在经济上可接受的成本下以工业规模生产微载体培养物的产品——即灭活脊髓灰质炎疫苗(IPV)仅仅十年后,人们对这种革命性的细胞生长系统产生了兴趣。其基本思路是开发一种具有同等潜力的培养系统,能够控制环境培养条件,并能够像工业微生物学中使用的系统那样进行放大。虽然最初只使用带正电荷的珠粒,但很快就清楚了,带负电荷或两性的物质,如蛋白质或氨基酸聚合到表面上同样有用。最终开发了许多不同类型的微载体。第二代微载体由大孔珠粒组成,通过外部和内部空间为细胞附着和生长提供了更大的表面积。这种微载体为某些生产系统(尤其是重组 CHO 细胞)提供了高细胞密度和提高生产力的巨大潜力。这些载体不仅为锚定依赖性细胞提供了可能性,也为悬浮生长的细胞提供了可能性,它们可以在均相生物反应器以及流化床或固定床系统中使用。尽管在微载体的开发和改进方面进行了大量投资和研究,但仍有一个问题悬而未决:微载体技术是否仍处于起步阶段,还是已经成熟,其基本思路是否已经实现?本文将对微载体技术的现状及其前景进行概述。