Supraphysiological Oxygen Levels in Mammalian Cell Culture: Current State and Future Perspectives

Area of Science:

• Cell Biology
• Physiology
• Biochemistry

Background:

• Conventional cell incubators maintain oxygen levels (~18%) significantly higher than physiological conditions in human tissues (2-6% physioxia).
• These supraphysiological oxygen conditions, termed hyperoxia, are increasingly recognized to influence fundamental cellular processes.

Purpose of the Study:

• To review the multifaceted effects of hyperoxia on cellular functions and redox homeostasis.
• To examine how hyperoxic cell culture fails to accurately model in vivo tissue physiology and pathology.
• To emphasize the importance of physioxia for reliable cell culture research.

Main Methods:

• Literature review of studies investigating the impact of varying oxygen concentrations on cell culture.
• Analysis of evidence detailing cellular responses under hyperoxic versus physioxic conditions.
• Synthesis of data on how oxygen levels affect gene expression, metabolism, and cellular responses.

Main Results:

• Supraphysiological oxygen levels significantly alter reactive oxygen species (ROS) metabolism, redox balance, gene expression, and mitochondrial dynamics.
• Hyperoxic cultures do not accurately reflect in vivo cellular behavior, impacting responses to drugs, hormones, and toxicants.
• Cellular respiration and replicative lifespan are demonstrably affected by oxygen tension.

Conclusions:

• Maintaining physioxia (2-6% O2) in cell culture is crucial for replicating in vivo tissue physiology and pathology.
• Failure to use physioxic conditions introduces research artifacts and hinders accurate translation of findings.
• Physioxia is imperative for advancing cell culture-based research and understanding disease mechanisms.