As indicated earlier, animal cell cultures also follow the same basic pattern of pattern growth as microbial cultures and enter a stationary phase. Although cells may be physically damaged by extreme culture conditions, resulting in necrosis, the more Common explanation of cessation of growth is apoptosis or PCD. This is regulated cellular process in response to nutrient deprivation or metabolite accumulation. The phenomenon can be limited by the addition of fresh medium (see later discussion of continuous and fed-batch culture) or supplementing the medium with antiapoptotic additives such as insulin growth factor (Butler, 2005, 2012). Chon and ZarbisPapastoitsis (2011) reported that the development of media free of animal-derived components have resulted in significantly increased viable cell densities—with reports of more than 1.5 × 107 cells cm−3 being achieved. Cell lines may also be genetically modified by inserting antiapoptotic genes, thus reducing the expression of the programmed cell death cascade (Butler, 2005, 2012). These aspects are discussed in Chapters 4 and 12.
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