Cell death in culture: Molecular mechanisms, detections, and inhibition strategies

Mammalian cell cultures are widely used in the biopharmaceutical industry to produce monoclonal antibodies, vaccines, growth factors, etc. Cell death is an essential biological process for physiological growth and development, but it is a major problem in biopharmaceutical production in bio-industry. Cell death within bioreactor occurs due to various intracellular and extracellular stresses. These stresses negatively affect the culture longevity, overall product quality, and yield. Among all cell death types, apoptosis accounts for most of the cellular death in the bioreactor. The implementation and development of various strategies to prevent the cellular death are crucial for robust bioprocess development. Cell death during culture can be prevented or inhibited by supplementing media with specific chemicals, synthetic inhibitors, and genetic cell engineering approaches. In this review, we classified and described different types of cell death and their molecular mechanisms and summarized the cell death inhibition approaches implemented to inhibit cell death for various applications.