Trends

Several examples given in the preceding sections already point toward activities undertaken to optimize animal cell technology and bioproducts of interest.

Cell lines other than the well-established hamster lines CHO and BHK present valuable alternatives, for example, the efficient production of recombinant proteins. Concomitant with an increasing understanding of media formulations, bioreactor design, and processes, efficiency and quality are still subject to improvement. Tailored cell lines can be selected by appropriate cloning strategies, using either naturally occurring variants or conferring specific characteristics by recombinant DNA methods (33).

The development of vectors with a predictable integration site for foreign DNA into the host genomic structure, including efficient expression systems, can overcome low-productivity problems. An example for enhanced productivity is the oncogene-activated system applied by Ternya et al. (83), where cells are cotransfected with the ras on-cogene.

Recombinant DNA technology gives new directions for the design of therapeutics with improved or even novel characteristics compared to their natural counterparts (e.g., pharmacokinetic properties). Ahern et al. (84) investigated recombinant variants of tPA produced by site-directed mutagenesis and identified proteins with increased fibrinolytic activity in vitro and decreased clearance in vivo.

New technologies, such as the encapsulation of cells, genetically engineered or as primary isolates, and transplantation into patients with various disorders or illnesses, could provide a cellular therapy tool for long-term treatment or even cure (85).

Other approaches attempt to simulate the three-dimensional microenvironment for constructing organotypical systems, such as artificial liver support devices (86) or drug metabolism studies (87). Investigations into the involvement of cytokines, extracellular matrixes, and cell-cell interactions are required to optimize organ models and lead to successful applications.

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