Apoptosis: A mammalian cell bioprocessing perspective

Area of Science:

• Biotechnology and Bioprocess Engineering
• Cell Biology
• Molecular Biology

Background:

• Apoptosis, a critical form of programmed cell death, significantly influences cell culture longevity and product quality in bioprocesses.
• Cellular stress within bioreactors is a primary instigator of apoptosis, necessitating a deeper understanding for process optimization.
• Mitigating apoptosis is essential for robust bioprocess development and ensuring consistent product yield and quality.

Purpose of the Study:

• To review apoptosis from a bioprocess engineering perspective, detailing its mechanisms and triggers.
• To explore strategies for avoiding cell death in bioreactors, focusing on industrially relevant cell lines.
• To highlight anti-apoptosis approaches, including cell engineering and model-based optimization for quality-by-design bioprocesses.

Main Methods:

• Literature review of apoptosis mechanisms and their links to bioreactor stresses.
• Analysis of operating conditions and their impact on cell viability.
• Examination of cell engineering and bioprocess optimization strategies to reduce apoptosis.

Main Results:

• Apoptosis is triggered by various stresses in bioreactors, affecting culture performance.
• Specific apoptotic pathways are identified and correlated with common bioprocess challenges.
• Effective strategies for controlling apoptosis include optimizing process parameters and employing cell engineering techniques.

Conclusions:

• Understanding and controlling apoptosis is crucial for enhancing bioprocess efficiency and product quality.
• Implementing anti-apoptosis strategies, from clone selection to large-scale production, is vital for quality-by-design biomanufacturing.
• Model-based optimization and cell engineering offer promising avenues for robust bioprocess development by minimizing cell death.