Meuwly F, Ruffieux P-A, Kadouri A, von Stockar U
Serono Biotech Center, Laboratoires Serono S.A., Zone Industrielle B, CH-1809 Fenil-sur-Corsier, Switzerland.
Biotechnol Adv. 2007 Jan-Feb;25(1):45-56. doi: 10.1016/j.biotechadv.2006.08.004. Epub 2006 Aug 30.
This article describes the development history of packed-bed bioreactors (PBRs) used for the culture of mammalian cells. It further reviews the current applications of PBRs and discusses the steps forward in the development of these systems for bioprocess and biomedical applications. The latest generation of PBRs used in bioprocess applications achieve very high cell densities (>10(8) cells ml(-1)) leading to outstandingly high volumetric productivity. However, a major bottleneck of such PBRs is their relatively small volume. The current maximal volume appears to be in the range of 10 to 30 l. A scale-up of more than 10-fold would be necessary for these PBRs to be used in production processes. In biomedical applications, PBRs have proved themselves as compact bioartificial organs, but their metabolic activity declines frequently within 1 to 2 weeks of operation. A main challenge in this field is to develop cell lines that grow consistently to high cell density in vitro and maintain a stable phenotype for a minimum of 1 to 2 months. Achieving this will greatly enhance the usefulness of PBR technology in clinical practice.
本文描述了用于哺乳动物细胞培养的填充床生物反应器（PBR）的发展历程。它进一步回顾了PBR的当前应用，并讨论了这些系统在生物工艺和生物医学应用开发方面的进展。用于生物工艺应用的最新一代PBR可实现非常高的细胞密度（>10⁸个细胞/毫升），从而带来极高的体积生产率。然而，此类PBR的一个主要瓶颈是其体积相对较小。目前的最大体积似乎在10至30升的范围内。要将这些PBR用于生产过程，扩大规模超过10倍将是必要的。在生物医学应用中，PBR已证明自身可作为紧凑型生物人工器官，但它们的代谢活性在运行1至2周内经常下降。该领域的一个主要挑战是开发能够在体外持续生长至高密度细胞并至少维持1至2个月稳定表型的细胞系。实现这一点将极大地提高PBR技术在临床实践中的实用性。
