Biochemical engineering animal cells

Bliem R Katinger H (1988) Scale-up engineering in animal cell technology Part II. Trends in Biotechnology 6 224-230. Bliem R, Konopitzky K Katinger H (1991) Industrial animal cell reactor systems aspects of selection and evaluation. Advances in Biochemical Engineering 44 2-26. 

For large-scale operations, biochemical engineers work with biological scientists to (1) obtain the best biological catalyst (microorganism, animal cell, plant cell, or enzyme) for a desired process,... 

Grampp G E, Sambanis A, Stephanopoulos G N (1992). Use of regulated secretion in protein production from animal cells An overview. Adv. Biochem. Engin. Biotechnol. 46 35-62. 

A CCA is a physical replica of the structure of a PBPK where cells or engineered tissues are used in organ compartments to achieve the metabolic and biochemical characteristics of the animal. Cell culture medium circulates between compartments and acts as a blood surrogate. Small-scale bioreactors with the appropriate cell types in the physical device represent organs or tissues. 

Dnring the period since World War II, collaborations between biochemists, applied microbiologists, and chemical engineers have evolved in several complementary directions, as their joint efforts have led to the successful development of innovative processes based on biochemical transformations that take place in creatively designed fermenters and bioreactors. This equipment has been tailormade to satisfy not only the safety, sanitation, and microbiological constraints imposed by the FDA and its counterparts in other nations, but also the labile and shear-sensitive nature of animal and plant cells. The equipment used in traditional facilities for manufacturing biopharmaceutical products consists of stainless steel bioreactors/fermenters, tanks, piping, valves, and so on, that are quasi permanent installations. 

A major limitation on the use of cell cultures is that isolated cells do not fuUy represent the full range of biochemical activity of the corresponding cell type when in a whole animal. Engineered tissues, especially cocultures [Bhatia et al., 1998], can provide a more natural environment, which can improve (i.e., make normal) cell function. Another alternative is the use of tissue slices, typically from the liver [Olinga et al, 1997]. Tissue sHces require the sacrifice of the animal there is intrinsic variability, and biochemical activities can decay rapidly after harvest. The use of isolated tissue slices also does not reproduce interchange of metaboHtes among organs and the time-dependent exposure that occurs within an animal. 

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