As cells generally continue to divide in culture, they generally grow to fill the available area or volume. This can generate several issues:
- Nutrient depletion in the growth media
- Accumulation of apoptotic/necrotic (dead) cells
- Cell-to-cell contact can stimulate cell cycle arrest, causing cells to stop dividing, known as contact inhibition.
- Cell-to-cell contact can stimulate cellular differentiation.
- Genetic and epigenetic alterations, with a natural selection of the altered cells potentially leading to overgrowth of abnormal, culture-adapted cells with decreased differentiation and increased proliferative capacity.
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