Life and death in mammalian cell culture: strategies for apoptosis inhibition

Mammalian cell culture is widely used to produce valuable biotherapeutics including monoclonal antibodies, vaccines and growth factors. Industrial cell lines such as Chinese hamster ovary (CHO), mouse myeloma (NS0), baby hamster kidney (BHK) and human embryonic kidney (HEK)-293 retain many molecular components of the apoptosis cascade. Consequently, these cells often undergo programmed cell death upon exposure to stresses encountered in bioreactors. The implementation of strategies to control apoptosis and enhance culture productivities represents a major goal of biotechnologists. Fortunately, previous research has uncovered many intracellular proteins involved in activating and inhibiting apoptosis. Here, we summarize three apoptotic pathways and discuss different environmental and genetic methodologies implemented to limit cell death for biotechnology applications.