Host Organisms Mammalian Cells

A variety of different cell lines is used today. One group consists of tissue derivatives, originally not showing amplified protein secretion [5]. Examples are Chinese hamster ovary (CHO) [6] or kidney cells like baby hamster kidney (BHK) 

Industrial Biotechnology Microorganisms, First Edition. Edited by Christoph Wittmann and James C. Liao. 

For the sake of brevity and considering given scientific and economic developments, this contribution focuses on CHO cells as one of the major players in mammalian-cell-based biopharmaceutical production. Unless otherwise stated, these cells are discussed and - where necessary - compared to alternative mammalian production systems. 

One of the characteristic features of mammalian cells in contrast to bacteria is their compartmented structure. Due to the existence of various cell organelles, for example, nucleus, mitochondrion, endoplasmic reticulum (ER), and Golgi apparatus, mammaUan cells are divided into compartments with specific functions. Nevertheless, several transport mechanisms form connections between the different compartments and show that local processes are part of a global cellular network. This chapter focuses on the basics of cellular structure and metabolism in the context of the global cellular network. 

In comparison to bacteria, CHO cells are growing slower and are significantly larger in size. When CHO cells are cultivated in suspension, they show growth 

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Host Cell Impurities Various organisms have been used to produce recombinant proteins yeast, bacteria (e.g., E. coli), insect cells, and mammalian cells such as Chinese hamster ovary (CHO) cells. During the purification process, some HCPs can copurify with the protein product. Because of the specificity of the antigen-antibody interaction, an ELISA can be used to detect and quantitate the contaminating HCPs. Detecting host impurities is important for quality process control as well as for product safety issues. The intent is to avoid unsafe levels of residual HCPs which might lead to adverse reactions.11... 

In addition to the differences in phospholipid content between microbial and host cell membranes, it has been demonstrated that disparity exists between the transmembrane potentials of both organisms. The transmembrane potential is defined by the proton flux between the inner and outer bilayers of the cytoplasmic membrane and ranges from —90 to —110 mV in normal mammalian cells in contrast to transmembrane potentials of —130 to —150mV for logarithmic phase microbes. The differences in these electrochemical gradients have been postulated to drive the influx of peptides into the cell and thus act as a crucial barrier for defining host defense peptide selectivity. ... 

The use of microcapsules for a variety of biomedical and biological applications has been promoted for many years. Several biomedical micro-capsulc applications are in clinical use or have approached clinical use. One application is the use of air-tilled human albumin microcapsules as ultrasound contrast agents. Another biomedical application of tnicrocap-sules is the encapsulation of live mammalian cells for transplantation into humans. The purpose of encapsulation is to protect the transplanted cells or organisms from rejection by the host. 

Bacterial membranes have a much more complex construction than mammalian membranes. This enables bacteria to survive in the various environments of host organisms. Knowledge of the composition and functioning of bacterial membranes is therefore essential to the development of anti-infective drugs. In order to be effective, antibacterial agents not only have to have optimal pharmacokinetic properties such as uptake and distribution in the patient, but they must also be able to cross an additional barrier, the cell wall of the bacteria, so that they can reach the target site. This additional barrier is remarkable on account of its rigidity and permeability. The construction and structural uniqueness of this barrier is briefly described below. 

For the expression of recombinant food allergens, the genomic- or cDNA-derived clone is ligated into a vector and introduced into the host organism. Bacteria, yeast, plants, and mammalian cells can be host systems. 

Mode of action The drug reacts with sulfhydryl groups of various substances including enzymes in both the organism and host. Parasitic enzymes may be more sensitive than are those of the host. There is evidence that mammalian cells may be less permeable to the drug and thus protected from its toxic effects. 

The vast majority of microorganisms of interest in pharmacy and medicine can be cultivated in the la b-oratory and most of them require relatively simple techniques and facilities. Some organisms are parasites and so can only be grown inside the cells of a host species — which often necessitates mammalian cell culture facilities— and there are a few (e.g. the organism responsible for leprosy) that have never been cultivated outside the living animal. 

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