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

Most conventional incubators used in cell culture do not regulate O-2 levels, making the headspace O-2 concentration similar to 18%. In contrast, most human tissues are exposed to 2-6% O-2 (physioxia) in vivo. Accumulating evidence has shown that such hyperoxic conditions in standard cell culture practices affect a variety of biological processes. In this review, we discuss how supraphysiological O-2 levels affect reactive oxygen species (ROS) metabolism and redox homeostasis, gene expression, replicative lifespan, cellular respiration, and mitochondrial dynamics. Furthermore, we present evidence demonstrating how hyperoxic cell culture conditions fail to recapitulate the physiological and pathological behavior of tissues in vivo, including cases of how O-2 alters the cellular response to drugs, hormones, and toxicants. We conclude that maintaining physioxia in cell culture is imperative in order to better replicate in vivo-like tissue physiology and pathology, and to avoid artifacts in research involving cell culture.

Automated summary

Most conventional incubators used in cell culture do not regulate O-2 levels, which leads to a higher oxygen concentration compared to the physiological conditions in human tissues. This review discusses the effects of supraphysiological O-2 levels on various biological processes and emphasizes the importance of maintaining physiological oxygen levels in cell culture to better replicate in vivo-like tissue physiology and pathology and to avoid artifacts in research involving cell culture.