Phases cell growth

Normal cells in culture show a sigmoid pattern of proliferative activity that reflects culture adaptation, environmental conditioning, nutrient availability and, for adherent cells, available free adhesion surface. 

Normal animal cell growth curve pattern, in which p is the specific cell growth rate. Lag phase (A) represents the culture adaptation period, followed by an exponential cell growth phase (B) until the attainment of a stationary or plateau phase (C), in which there is no increase in cell number. The culture reaches the senescence phase (D) when the percentage of cells in division becomes lower than the percentage of cells dying. 

The lag phase occurs after cell inoculation. In this phase, there is no cell division or division takes place at low specific rates. It is an adaptation period in which adherent cells may resynthesize the glycocalyx elements lost during trypsinization, bind, and spread on the substratum. During spreading, the cytoskeleton reappears and new structural proteins are synthesized (Freshney, 2005). The duration of the lag phase is dependent on at least two factors the point in the growth phase from which cells were taken in the previous culture and the inoculum concentration. Cells originating from an actively growing culture have a shorter lag phase than those from a quiescent culture. Cultures initiated at low cell densities condition the culture medium more slowly and hence increase the duration of the lag phase, which is not desirable. 

Factors that influence the duration of the log phase are inoculum concentration, cell growth rate, nutrient availability, and accumulation of inhibitory metabolites. For adherent cells, the end of the log phase may also occur at confluence, when cells cover all the available growth surface, at which point contact inhibition restricts further growth. 

The stationary phase is followed by a decline period in which cell death is not compensated by cells in proliferation. Cell death can occur by two distinct mechanisms, named necrosis and apoptosis. Necrosis occurs as a result of an irreversible injury and normal homeostasis is lost. In vivo, this form of death generally affects the neighboring cells and may result in inflammation. Autodestruction occurs by activation of hydrolases when there is a lack of nutrients and oxygen, followed by progressive disorganization and complete disintegration of the cell. 

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Cell growth phases comprise lag phase, exponential or log growth phase, stationary or plateau phase, and senescence or death phase, as shown in Figure 2.5. Cell growth can be mathematically represented by the following general equation ... 

Mian, N., Analysis of cell-growth-phase-related variations in hyaluronate synthase activity of isolated plasma-membrane fractions of cultured human skin fibroblasts, Biochem. J., 237, 333, 1986. 

Levels of HA deposition respond to the various physiological states of the cell. In cultures of normal animal cells, growth phase [34], and degrees of confluence are inversely related to HA levels in both fibroblasts [106] and keratinocytes [38]. HA has been correlated with the onset of mitosis and detachment from the substratum [35], calcium concentrations [107], anoxia and lactate levels [108], viral transformation [109], and serum stimulation [110,111]. 

Bioconversion always begins with cultivation of the cells. For metabolite production the cell growth phase is followed by a production phase and for transformation of chemicals by the biochemical alteration of chemical compounds. 

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