Using cell engineering and omic tools for the improvement of cell culture processes

Abstract

Significant strides have been made in mammalian cell based biopharmaceutical process and cell line development over the past years. With several established mammalian host cell lines and expression systems, optimization of selection systems to reduce development times and improvement of glycosylation patterns are only some of the advances being made to improve cell culture processes. In this article, the advances pertaining to cell line development and cell engineering strategies are discussed. An overview of the cell engineering strategies to enhance cellular characteristics by genetic manipulation are illustrated, focusing on the use of genomics and proteomics tools and their application in such endeavors. Included in this review are some of the early studies using the 'omic' technique to understand cellular mechanisms of product synthesis and secretion, apoptosis, cell proliferation and the influence of the physicochemical environment. The article highlights the significance of integrating genomics and proteomics data with the vast amounts of bioprocess data for improved analysis of the biological pathways involved. Further improvements of the techniques and methodologies used are needed but ultimately, the new cell engineering strategies should provide great insight into the regulatory networks within the cell in a bioprocess environment and how to manipulate them to increase overall productivity.

Cell death in mammalian cell culture: molecular mechanisms and cell line engineering strategies

“…The importance of modification of the intracellular cell death pathways to enhance the robustness, survival and productivity of production cell lines has been suggested (Cohen and Al-Rubeai 1995) and demonstrated by several research groups in the last 15 years (reviewed by Kuystermans et al 2007) (Table 1).…”

“…The development and deployment of the 'omic' technologies (genomic, proteomic, metabolomic) to study cell death will certainly help to discover novel targets for cell death engineering (Kuystermans et al 2007;Wong et al 2006). Additionally, with the concept of cell death by autophagy in mind, it seems worthwhile to revisit the issue of cell death in production processes Zustiak et al 2008).…”

Establishment of a mammalian cell line suitable for industrial production of recombinant protein using mutations induced by high-energy beam radiation

“…Because of the increase in demand for therapeutic proteins, techniques to achieve higher productivity are required. Towards this goal, different approaches including host cell engineering have been developed (Fujita et al 1996;Kuystermans et al 2007;Chusainow et al 2009), as well as proliferation control using cytokines . Currently, CHO cells are extensively used in industry to produce therapeutic proteins, partly because they can provide stable and accurate glycosylation of proteins.…”

Chemostat‐based transcriptional analysis of growth rate change and BCL‐2 over‐expression in NS0 cells

“…The importance of molecular information on high cell specific productivity, correct product processing, cell proliferation or apoptosis prevention using ''omic'' technologies, is a key element in cell line development (Kuystermans et al, 2007;O'Callaghan and James, 2008). Increasingly, efforts have been made to probe transcriptomic and proteomic alterations between cells of different productivities (Charaniya et al, 2009;Khoo et al, 2007;Seth et al, 2007;Smales et al, 2004), culture conditions (Krampe et al, 2008;Shen et al, 2010;Swiderek and Al-Rubeai, 2007) or cells treated with chemical agents (Kantardjieff et al, 2010).…”