What media components can reduce apoptosis and increase cell viability beyond critical density?

Answer

Apoptosis is typically caused by nutrient depletion and/or metabolite accumulation. Nutrient depletion can be prevented by proper feeding strategies. Metabolite accumulation is less of concern in a perfusion process but is often challenging to tackle in a fed-batch process. Media optimization approaches to control the accumulation of metabolites may include: reducing glutamine to control ammonia, reducing bicarbonate to modulate carbon dioxide, and use of alternate carbon sources to control lactate levels. In addition, there are reports on targeting the apoptosis pathway by the incorporation of chemicals such as caspase inhibitors or the use of silencing RNA. However, these approaches have not been incorporated into industrial processes yet.

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